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Show:  Items 1-60 of 60 One page.

1: Genetics 2001 May;158(1):197-207 Related Articles, Books, Protein, Nucleotide, LinkOut
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Genes regulating touch cell development in Caenorhabditis elegans.

Du H, Chalfie M.

Department of Biological Sciences, Columbia University, 1012 Fairchild Ctr., New York, NY 10027, USA.

To identify genes regulating the development of the six touch receptor neurons, we screened the F(2) progeny of mutated animals expressing an integrated mec-2::gfp transgene that is expressed mainly in these touch cells. From 2638 mutated haploid genomes, we obtained 11 mutations representing 11 genes that affected the production, migration, or outgrowth of the touch cells. Eight of these mutations were in known genes, and 2 defined new genes (mig-21 and vab-15). The mig-21 mutation is the first known to affect the asymmetry of the migrations of Q neuroblasts, the cells that give rise to two of the six touch cells. vab-15 is a msh-like homeobox gene that appears to be needed for the proper production of touch cell precursors, since vab-15 animals lacked the four more posterior touch cells. The remaining touch cells (the ALM cells) were present but mispositioned. A similar touch cell phenotype is produced by mutations in lin-32. A more severe phenotype; i.e., animals often lacked ALM cells, was seen in lin-32 vab-15 double mutants, suggesting that these genes acted redundantly in ALM differentiation. In addition to the touch cell abnormalities, vab-15 animals variably exhibit embryonic or larval lethality, cell degenerations, malformation of the posterior body, uncoordinated movement, and defective egg laying.

PMID: 11333230 [PubMed - indexed for MEDLINE]

2: Genes Dev 2001 Mar 15;15(6):789-802 Related Articles, Books, LinkOut
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Inhibition of touch cell fate by egl-44 and egl-46 in C. elegans.

Wu J, Duggan A, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

In wild-type Caenorhabditis elegans, six cells develop as receptors for gentle touch. In egl-44 and egl-46 mutants, two other neurons, the FLP cells, express touch receptor-like features. egl-44 and egl-46 also affect the differentiation of other neurons including the HSN neurons, two cells needed for egg laying. egl-44 encodes a member of the transcription enhancer factor family. The product of the egl-46 gene, two Drosophila proteins, and two proteins in human and mice define a new family of zinc finger proteins. Both egl-44 and egl-46 are expressed in FLP and HSN neurons (and other cells); expression of egl-46 is dependent on egl-44 in the FLP cells but not in the HSN cells. Wild-type touch cells express egl-46 but not egl-44. Moreover, ectopic expression of egl-44 in the touch cells prevents touch cell differentiation in an egl-46-dependent manner. The sequences of these genes and their nuclear location as seen with GFP fusions indicate that they repress transcription of touch cell characteristics in the FLP cells.

PMID: 11274062 [PubMed - indexed for MEDLINE]

3: Nature 1999 May 13;399(6732):162-6 Related Articles, Books, Protein, Nucleotide, LinkOut
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A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants.

Taub J, Lau JF, Ma C, Hahn JH, Hoque R, Rothblatt J, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

The dauer larva is an alternative larval stage in Caenorhabditis elegans which allows animals to survive through periods of low food availability. Well-fed worms live for about three weeks, but dauer larvae can live for at least two months without affecting post-dauer lifespan. Mutations in daf-2 and age-1, which produce a dauer constitutive (Daf-C) phenotype, and in clk-1, which are believed to slow metabolism, markedly increase adult lifespan. Here we show that a ctl-1 mutation reduces adult lifespan in otherwise wild-type animals and eliminates the daf-c and clk-1-mediated extension of adult lifespan. ctl-1 encodes an unusual cytosolic catalase; a second gene, ctl-2, encodes a peroxisomal catalase. ctl-1 messenger RNA is increased in dauer larvae and adults with the daf-c mutations. We suggest that the ctl-1 catalase is needed during periods of starvation, as in the dauer larva, and that its misexpression in daf-c and clk-1 adults extends lifespan. Cytosolic catalase may have evolved to protect nematodes from oxidative damage produced during prolonged dormancy before reproductive maturity, or it may represent a general mechanism for permitting organisms to cope with the metabolic changes that accompany starvation.

PMID: 10335847 [PubMed - indexed for MEDLINE]

4: Nature 1998 Dec 17;396(6712):620-1 Related Articles, Books, LinkOut
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Genome sequencing. The worm revealed.

Chalfie M.

Publication Types:
  • News

PMID: 9872304 [PubMed - indexed for MEDLINE]

5: J Neurosci 1999 Jan 1;19(1):159-67 Related Articles, Books, LinkOut
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EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in caenorhabditis elegans.

Lee RY, Sawin ER, Chalfie M, Horvitz HR, Avery L.

Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9148, USA.

The Caenorhabditis elegans gene eat-4 affects multiple glutamatergic neurotransmission pathways. We find that eat-4 encodes a protein similar in sequence to a mammalian brain-specific sodium-dependent inorganic phosphate cotransporter I (BNPI). Like BNPI in the rat CNS, eat-4 is expressed predominantly in a specific subset of neurons, including several proposed to be glutamatergic. Loss-of-function mutations in eat-4 cause defective glutamatergic chemical transmission but appear to have little effect on other functions of neurons. Our data suggest that phosphate ions imported into glutamatergic neurons through transporters such as EAT-4 and BNPI are required specifically for glutamatergic neurotransmission.

PMID: 9870947 [PubMed - indexed for MEDLINE]

6: Trends Genet 1998 Dec;14(12):506-12 Related Articles, Books, LinkOut
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C. elegans neuroscience: genetics to genome.

Chalfie M, Jorgensen EM.

Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027, USA.

From their earliest experiments, researchers using Caenorhabditis elegans have been interested in the role of genes in the development and function of the nervous system. As the C. elegans Genome Project completes the genomic sequence, we review the accomplishments of these researchers and the impact that the Genome Project has bad on their research. We also speculate on future directions in this research that are enabled by the efforts of the Genome Project.

Publication Types:
  • Review
  • Review, tutorial

PMID: 9865157 [PubMed - indexed for MEDLINE]

7: Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15492-5 Related Articles, Books, Protein, Nucleotide, LinkOut
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Two functionally dependent acetylcholine subunits are encoded in a single Caenorhabditis elegans operon.

Treinin M, Gillo B, Liebman L, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

The deg-3 gene from the nematode Caenorhabditis elegans encodes an alpha subunit of a nicotinic acetylcholine receptor that was first identified by a dominant allele, u662, which produced neuronal degeneration. Because deg-3 cDNAs contain the SL2 trans-spliced leader, we suggested that deg-3 was transcribed as part of a C. elegans operon. Here we show that des-2, a gene in which mutations suppress deg-3(u662), is the upstream gene in that operon. The des-2 gene also encodes an alpha subunit of a nicotinic acetylcholine receptor. As expected for genes whose mRNAs are formed from a single transcript, both genes have similar expression patterns. This coexpression is functionally important because (i) des-2 is needed for the deg-3(u662) degenerations in vivo; (ii) an acetylcholine-gated channel is formed in Xenopus oocytes when both subunits are expressed but not when either is expressed alone; and (iii) channel activity, albeit apparently altered from that of the wild-type channel, results from the expression of a u662-type mutant subunit but, again, only when the wild-type DES-2 subunit is present. Thus, the operon structure appears to regulate the coordinate expression of two channel subunits.

PMID: 9860996 [PubMed - indexed for MEDLINE]

8: Development 1998 Oct;125(20):4107-19 Related Articles, Books, LinkOut
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Regulation of touch receptor differentiation by the Caenorhabditis elegans mec-3 and unc-86 genes.

Duggan A, Ma C, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

The nematode Caenorhabditis elegans possesses six morphologically similar neurons that are responsible for sensing gentle touch to the body. Previous genetic studies identified genes that are necessary for the production and differentiation of these touch cells. In particular, unc-86 encodes a POU-type homeodomain protein needed for the production of the touch cells, while mec-3 encodes a LIM-type homeodomain protein needed for the differentiation of the touch cells. Molecular studies showed that MEC-3 and UNC-86 bind cooperatively to sites in the mec-3 promoter and can synergistically activate transcription from it in vitro. Here we show that UNC-86::MEC-3 hetero-oligomer-binding sites are also found in the promoters of two presumed targets of mec-3, the mec-4 and mec-7 genes, that are necessary for the function of the touch cells. These sites, which are well-conserved in the related nematode C. briggsae, are required for promoter activity. When one of the binding sites is cloned into a heterologous promoter, expression is found in the touch cells and two to four other cells that express mec-3 and unc-86. These data support a model in which touch-cell differentiation is specified, in part, by the UNC-86::MEC-3 hetero-oligomer and not by MEC-3 alone. Ectopic expression of mec-3, driven by a heat-shock promoter, also supports this hypothesis: the acquisition of touch-cell characteristics by several additional cells under these conditions required unc-86. Since the touch-cell lineages express UNC-86 before MEC-3, MEC-3 appears to modify the activity of UNC-86, leading to touch-cell-specific gene expression. Because both UNC-86 and MEC-3 have activation domains, the formation of the hetero-oligomer may create a strong activator. In the modification of UNC-86 function by MEC-3 in the touch cells, these studies provide an example of how the sequential activation of transcription factors can determine cell fate within particular cell lineages.

PMID: 9735371 [PubMed - indexed for MEDLINE]

9: Trends Genet 1997 Mar;13(3):94-5 Related Articles, Books, LinkOut

Is the traditional way of teaching three-factor mapping sufficient?

Chalfie M.

Publication Types:
  • Letter

PMID: 9066267 [PubMed - indexed for MEDLINE]

10: J Neurosci 1997 Feb 1;17(3):1033-45 Related Articles, Books, LinkOut
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Neuropathology of degenerative cell death in Caenorhabditis elegans.

Hall DH, Gu G, Garcia-Anoveros J, Gong L, Chalfie M, Driscoll M.

Department of Neurosciences, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

In Caenorhabditis elegans necrosis-like neuronal death is induced by gain-of-function (gf) mutations in two genes, mec-4 and deg-1, that encode proteins similar to subunits of the vertebrate amiloride-sensitive epithelial Na+ channel. We have determined the progress of cellular pathology in dying neurons via light and electron microscopy. The first detectable abnormality is an infolding of the plasma membrane and the production of small electron-dense whorls. Later, cytoplasmic vacuoles and larger membranous whorls form, and the cell swells. More slowly, chromatin aggregates and the nucleus invaginates. Mitochondria and Golgi are not dramatically affected until the final stages of cell death when organelles, and sometimes the cells themselves, lyse. Certain cells, including some muscle cells in deg-1 animals, express the abnormal gene products and display a few membrane abnormalities but do not die. These cells either express the mutant genes at lower levels, lack other proteins needed to form inappropriately functioning channels, or are better able to compensate for the toxic effects of the channels. Overall, the ultrastructural changes in these deaths suggest that enhanced membrane cycling precedes vacuolation and cell swelling. The pathology of mec-4(gf) and deg-1(gf) cells shares features with that of genetic disorders with alterations in channel subunits, such as hypokalemic periodic paralysis in humans and the weaver mouse, and with degenerative conditions, e.g., acute excitotoxic death. The initial pathology in all of these conditions may reflect attempts by affected cells to compensate for abnormal membrane proteins or functions.

PMID: 8994058 [PubMed - indexed for MEDLINE]

11: Proc Natl Acad Sci U S A 1996 Jun 25;93(13):6577-82 Related Articles, Books, LinkOut
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Genetic interactions affecting touch sensitivity in Caenorhabditis elegans.

Gu G, Caldwell GA, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

At least 13 genes (mec-1, mec-2, mec-4-10, mec-12, mec-14, mec-15, and mec-18) are needed for the response to gentle touch by 6 touch receptor neurons in the nematode Caenorhabditis elegans. Several, otherwise recessive alleles of some of these genes act as dominant enhancer mutations of temperature-sensitive alleles of mec-4, mec-5, mec-6, mec-12, and mec-15. Screens for additional dominant enhancers of mec-4 and mec-5 yielded mutations in previously known genes. In addition, some mec-7 alleles showed allele-specific, dominant suppression of the mec-15 touch-insensitive (Mec) phenotype. The dominant enhancement and suppression exhibited by these mutations suggest that the products of several touch genes interact. These results are consistent with a model, supported by the known sequences of these genes, that almost all of the touch function genes contribute to the mechanosensory apparatus.

PMID: 8692859 [PubMed - indexed for MEDLINE]

12: J Cell Biol 1996 Jun;133(5):1071-81 Related Articles, Books, Protein, Nucleotide

Sequence and transmembrane topology of MEC-4, an ion channel subunit required for mechanotransduction in Caenorhabditis elegans.

Lai CC, Hong K, Kinnell M, Chalfie M, Driscoll M.

Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, 08855, USA.

The process by which mechanical stimuli are converted into cellular responses is poorly understood, in part because key molecules in this mode of signal transduction, the mechanically gated ion channels, have eluded cloning efforts. The Caenorhabditis elegans mec-4 gene encodes a subunit of a candidate mechanosensitive ion channel that plays a critical role in touch reception. Comparative sequence analysis of C. elegans and Caenorhabditis briggsae mec-4 genes was used to initiate molecular studies that establish MEC-4 as a 768-amino acid protein that includes two hydrophobic domains theoretically capable of spanning a lipid bilayer. Immunoprecipitation of in vitro translated mec-4 protein with domain-specific anti-MEC-4 antibodies and in vivo characterization of a series of mec-4lacZ fusion proteins both support the hypothesis that MEC-4 crosses the membrane twice. The MEC-4 amino- and carboxy-terminal domains are situated in the cytoplasm and a large domain, which includes three Cys-rich regions, is extracellular. Definition of transmembrane topology defines regions that might interact with the extracellular matrix or cytoskeleton to mediate mechanical signaling.

PMID: 8655580 [PubMed - indexed for MEDLINE]

13: Neuron 1996 Jan;16(1):183-94 Related Articles, Books, Protein, Nucleotide, LinkOut
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Extracellular proteins needed for C. elegans mechanosensation.

Du H, Gu G, William CM, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

The mec-5 and mec-9 genes encode putative extracellular proteins that allow a set of six touch receptor neurons in C. elegans to respond to gentle touch. MEC-5 is a collagen made by the epidermal cells that surround the touch cells. Mutations causing touch insensitivity affect the Gly-X-Y repeats of this collagen. mec-9 produces two transcripts, the larger of which is expressed in the touch cells and two PVD neurons. This transcript encodes a protein with 5 Kunitz-type protease inhibitor domains, 6 EGF-like repeats (2 of the Ca(2+)-binding type), and a glutamic acid-rich region. Missense mutations causing touch insensitivity affect both the EGF-like and Kunitz domains. Since mec-9 loss of function mutations dominantly enhance the touch insensitive phenotype of several mec-5 mutations, MEC-5 and MEC-9 may interact. We propose that these proteins provide an extracellular attachment point for the mechanosensory channels of the touch cells.

PMID: 8562083 [PubMed - indexed for MEDLINE]

14: Nature 1995 Nov 16;378(6554):292-5 Related Articles, Books, Protein, Nucleotide

A stomatin-like protein necessary for mechanosensation in C. elegans.

Huang M, Gu G, Ferguson EL, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

The mec-2 gene is required for the function of a set of six touch receptor neurons in the nematode Caenorhabditis elegans; mec-2 mutants, which are touch-insensitive, have touch cells that appear morphologically normal. Gene interaction studies suggest that mec-2 positively regulates the activity of the putative mechanosensory transduction channel (and the present paper), comprised in part of proteins encoded by the two degenerin genes mec-4 and mec-10 The central region of the mec-2 protein (MEC-2) is very similar to stomatin, an integral membrane protein (band 7.2b) in human red blood cells that is thought to regulate cation conductance. MEC-2-LacZ fusions are distributed along the touch receptor axons. This axonal distribution, which is mediated by the mec-2-specific amino terminus, is disrupted by mutations in mec-12, an alpha-tubulin gene needed for touch cell function. Our results indicate that MEC-2 links the mechanosensory channel and the microtubule cytoskeleton of the touch receptor neurons. Such linkage provides the basis for a mechanism of mechanosensation whereby microtubule displacement leads to channel opening.

PMID: 7477350 [PubMed - indexed for MEDLINE]

15: Science 1995 Oct 20;270(5235):415-30 Related Articles, Books, LinkOut

Genome maps. VI. Caenorhabditis elegans. Wall chart.

Chalfie M, Eddy S, Hengartner MO, Hodgkin J, Kohara Y, Plasterk RH, Waterston RH, White JG.

Columbia University, New York, NY, USA.

PMID: 7569996 [PubMed - indexed for MEDLINE]

16: Photochem Photobiol 1995 Oct;62(4):651-6 Related Articles, Books

Green fluorescent protein.

Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

Several bioluminescent coelenterates use a secondary fluorescent protein, the green fluorescent protein (GFP), in an energy transfer reaction to produce green light. The most studied of these proteins have been the GFPs from the jellyfish Aequorea victoria and the sea pansy Renilla reniformis. Although the proteins from these organisms are not identical, they are thought to have the same chromophore, which is derived from the primary amino acid sequence of GFP. The differences are thought to be due to changes in the protein environment of the chromophore. Recent interest in these molecules has arisen from the cloning of the Aequorea gfp cDNA and the demonstration that its expression in the absence of other Aequorea proteins results in a fluorescent product. This demonstration indicated that GFP could be used as a marker of gene expression and protein localization in living and fixed tissues. Bacterial, plant and animal (including mammalian) cells all express GFP. The heterologous expression of the gfp cDNA has also meant that it could be mutated to produce proteins with different fluorescent properties. Variants with more intense fluorescence or alterations in the excitation and emission spectra have been produced.

Publication Types:
  • Review
  • Review, tutorial

PMID: 7480149 [PubMed - indexed for MEDLINE]

17: Neuron 1995 Apr;14(4):871-7 Related Articles, Books, Protein, Nucleotide, LinkOut
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A mutated acetylcholine receptor subunit causes neuronal degeneration in C. elegans.

Treinin M, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Neurotoxicity through abnormal activation of membrane channels is a potential cause of neurodegenerative disease. Here we show that a gain-of-function mutation, deg.3(u662), leads to the degeneration of a small set of neurons in the nematode C. elegans. The deg.3 gene encodes a nicotinic acetylcholine receptor alpha subunit, which in the region of transmembrane domain II is most similar to the neuronal alpha 7 subunits from rat and chicken. The u662 mutation changes a residue in the second transmembrane domain, the domain thought to form the channel pore. A similar change in the equivalent amino acid in the chick protein produces channels that desensitize slowly. Channel hyperactivity may underlie the degenerations seen in the C. elegans deg.3(u662) mutants, since antagonists of nicotinic acetylcholine receptors suppress the deg-3(u662) mutant phenotypes.

PMID: 7718248 [PubMed - indexed for MEDLINE]

18: Curr Biol 1995 Apr 1;5(4):441-8 Related Articles, Books, Protein, Nucleotide, LinkOut

Erratum in:
  • Curr Biol 1995 Jun 1;5(6):686
Click here to read
Regulation of Caenorhabditis elegans degenerin proteins by a putative extracellular domain.

Garcia-Anoveros J, Ma C, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

BACKGROUND: Rare, dominant mutations in the degenerin genes of Caenorhabditis elegans (deg-1, mec-4 and mec-10) cause neuronal degeneration. The extensive sequence similarity between degenerins and mammalian genes that encode subunits of the amiloride-sensitive sodium channel from kidney, colon and lung suggests that the C. elegans degenerins form ion channels. As mec-4 and mec-10 are needed for the reception of gentle touch stimuli, they may contribute to a mechanosensory ion channel. All the dominant degeneration-causing mutations in the C. elegans degenerin genes affect equivalent residues in a hydrophobic region that is structurally similar to the H5 domain of several ion channels, and so could form the channel lining. Increased channel activity may underlie the resulting degeneration, in which the affected cells vacuolate and swell. RESULTS: We now demonstrate that a missense change in a predicted extracellular region of the proteins encoded by deg-1 and mec-4 causes cell death similar to that caused by the dominant mutations. The missense mutation lies within a 22 amino-acid region found in all the C. elegans degenerins for which the sequences have been published, but not in the similar mammalian proteins. Deletion of nine amino acids surrounding the mutation site in mec-4 also causes neuronal degeneration. The degeneration-causing mutations in either the predicted pore-lining or the predicted extracellular regions of deg-1 are suppressed by additional, dominantly acting mutations that substitute larger for smaller residues within the channel lining. CONCLUSIONS: Our data suggest that the putative extracellular domain negatively regulates degenerin activity, perhaps by gating the channel. As this region is only found in the C. elegans proteins, it may allow more rapid regulation of the nematode channels, which may be needed for them to function in mechanosensation. The suppressor mutations, by adding larger amino acids to the putative pore lining, could prevent degeneration by blocking the pore of a multisubunit channel.

PMID: 7627559 [PubMed - indexed for MEDLINE]

19: Curr Opin Neurobiol 1995 Feb;5(1):6-9 Related Articles, Books, LinkOut
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Control of neuronal development in Caenorhabditis elegans.

Duggan A, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027, USA.

Recent research into the development of the nervous system of the nematode Caenorhabditis elegans indicates the importance of multiple cell interactions and combinatorial gene expression. As many of the genes needed for C. elegans neuronal development have counterparts with similar activities in Drosophila melanogaster, the mechanisms of cell specification may be broadly conserved.

Publication Types:
  • Review
  • Review, tutorial

PMID: 7773007 [PubMed - indexed for MEDLINE]

20: Prog Brain Res 1995;105:179-82 Related Articles, Books

The differentiation and function of the touch receptor neurons of Caenorhabditis elegans.

Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027, USA.

We have identified several genes required for four aspects of the differentiation and function of a set of six touch receptor neurons in the nematode Caenorhabditis elegans: (1) the generation of appropriate cells; (2) the specification of those cells to differentiate as touch receptors; (3) the maintenance of the differentiated state; and (4) the expression of products need for the cell function. Three major conclusions about the development of the touch cells arise from the analysis of these genes. First, specification of cell fate is a combinatorial process. At least seven genes, none of which are expressed solely in these cells, are needed to restrict the expression of touch-cell features in the appropriate cells. Second, the differentiated state must also be maintained. Three genes appear necessary for this maintenance function. Third, regulation of development is not strictly linear; at least one gene is needed at more than one stage of differentiation. In addition to being interested in the factor that determine cell fate, we are also interested in understanding the molecular basis of mechanosensory transduction. The function class genes are particularly important in this regard, especially those that when mutant result in the loss of the touch response without producing any obvious morphological defects in the touch cells.

Publication Types:
  • Review
  • Review, tutorial

PMID: 7568875 [PubMed - indexed for MEDLINE]

21: J Cell Sci 1994 Aug;107 ( Pt 8):2165-75 Related Articles, Books, LinkOut
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Mutations in the Caenorhabditis elegans beta-tubulin gene mec-7: effects on microtubule assembly and stability and on tubulin autoregulation.

Savage C, Xue Y, Mitani S, Hall D, Zakhary R, Chalfie M.

Department of Biological Sciences, Sherman Fairchild Center, Columbia University, New York, NY 10027.

We have sequenced 45 mutations in mec-7, a beta-tubulin gene required for the production of 15-protofilament microtubules in the nematode Caenorhabditis elegans, and have correlated sequence alterations with mutant phenotypes. The expression patterns of most alleles have also been determined by in situ hybridization and immunocytochemistry. Most (12/16) complete loss-of-function alleles, which are recessive, result from nonsense mutations, insertions, or deletions; three others disrupt a putative GTP-binding domain. Three of the four loss-of-function, missense mutations result in elevated mec-7 message levels, suggesting a defect in tubulin autoregulation that may be attributable to a loss in the ability to form heterodimers. Most (8/9) mild alleles are caused by missense mutations. Two mild alleles appear to increase microtubule stability and lead to the elaboration of ectopic neuronal processes in mec-7-expressing cells. Most (15/23) mutations that cause severe dominant or semidominant phenotypes are clustered into three discrete domains; four others occur in putative GTP-binding regions. Many of these dominant mutations appear to completely disrupt microtubule assembly.

PMID: 7983175 [PubMed - indexed for MEDLINE]

22: Science 1994 Feb 11;263(5148):802-5 Related Articles, Books, Nucleotide

Green fluorescent protein as a marker for gene expression.

Chalfie M, Tu Y, Euskirchen G, Ward WW, Prasher DC.

Department of Biological Sciences, Columbia University, New York, NY 10027.

A complementary DNA for the Aequorea victoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic (Escherichia coli) or eukaryotic (Caenorhabditis elegans) cells. Because exogenous substrates and cofactors are not required for this fluorescence, GFP expression can be used to monitor gene expression and protein localization in living organisms.

PMID: 8303295 [PubMed - indexed for MEDLINE]

23: Nature 1994 Feb 3;367(6462):467-70 Related Articles, Books, Protein, Nucleotide

Comment in:
  • Nature. 1994 Feb 3;367(6462):412-3

Gene interactions affecting mechanosensory transduction in Caenorhabditis elegans.

Huang M, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

Genetic screening has identified a group of mec (mechanosensory) genes that are required for the function of a set of six touch-receptor neurons in the nematode Caenorhabditis elegans. Such genes potentially encode components of the mechanosensory apparatus. We have cloned one of these genes, mec-10, which is a member of the degenerin gene family (genes such as mec-4 and deg-1 that can be mutated to cause neurodegeneration). Because components of an amiloride-sensitive sodium channel (alpha, beta and gamma rENaC) from rat share considerable sequence similarity with the C. elegans genes, it is likely that degenerins may function as channel proteins. Here we show that two degenerin homologues (mec-4 and mec-10) are expressed in the same cells, although each provides a unique function. Based on genetic data of mutations affecting mec-10-induced degeneration, we propose that the products of three genes (mec-4, mec-10 and mec-6) form a complex needed for mechanosensation, and that several other mec genes may be important in regulating the putative channel complex.

PMID: 7509039 [PubMed - indexed for MEDLINE]

24: Development 1993 Nov;119(3):773-83 Related Articles, Books, LinkOut
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Combinatorial control of touch receptor neuron expression in Caenorhabditis elegans.

Mitani S, Du H, Hall DH, Driscoll M, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027.

Six touch receptor neurons with distinctive morphological features sense gentle touch in Caenorhabditis elegans. Previous studies have identified three genes (lin-32, unc-86 and mec-3) that regulate touch cell development. However, since other cell types also require these genes, we suspected that other genes help restrict the expression of touch cell characteristics to the six neurons seen in the wild type. To identify such genes, we have examined mutants defective in genes required for the development of other C. elegans cells for changes in the pattern of touch cell-specific features. Mutations in seven genes either reduce (lin-14) or increase (lin-4, egl-44, egl-46, sem-4, ced-3 and ced-4) the number of touch receptor-like cells. The combinatorial action of these genes, all of which are required for the production of many cell types, restrict the number of cells expressing touch receptor characteristics in wild-type animals by acting as positive and negative regulators and by removing cells by programmed cell death.

PMID: 8187641 [PubMed - indexed for MEDLINE]

25: J Neurobiol 1993 Oct;24(10):1433-41 Related Articles, Books, LinkOut

Touch receptor development and function in Caenorhabditis elegans.

Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

Mutations causing a touch-insensitive phenotype in the nematode Caenorhabditis elegans have been the basis of studies on the specification of neuronal cell fate, inherited neurodegeneration, and the molecular nature of mechanosensory transduction.

Publication Types:
  • Review
  • Review, tutorial

PMID: 8228965 [PubMed - indexed for MEDLINE]

26: Science 1993 Sep 3;261(5126):1324-8 Related Articles, Books

Cooperative interactions between the Caenorhabditis elegans homeoproteins UNC-86 and MEC-3.

Xue D, Tu Y, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027.

The POU-type homeodomain protein UNC-86 and the LIM-type homeodomain protein MEC-3, which specify neuronal cell fate in the nematode Caenorhabditis elegans, bind cooperatively as a heterodimer to the mec-3 promoter. Heterodimer formation increases DNA binding stability and, therefore, increases DNA binding specificity. The in vivo significance of this heterodimer formation in neuronal differentiation is suggested by (i) a loss-of-function mec-3 mutation whose product in vitro binds DNA well but forms heterodimers with UNC-86 poorly and (ii) a mec-3 mutation with wild-type function whose product binds DNA poorly but forms heterodimers well.

PMID: 8103239 [PubMed - indexed for MEDLINE]

27: Curr Opin Genet Dev 1993 Apr;3(2):275-7 Related Articles, Books

Homeobox genes in Caenorhabditis elegans.

Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027.

It is estimated that approximately 60 homeobox genes occur in the nematode Caenorhabditis elegans. These genes are required for specifying the cell fate of both precursor and terminally differentiated cells. In some cases, highly specific cell functions, such as migration pattern or synaptic connectivity, require the action of these genes.

Publication Types:
  • Review
  • Review, tutorial

PMID: 8099297 [PubMed - indexed for MEDLINE]

28: Nature 1993 Feb 11;361(6412):504 Related Articles, Books

Comment on:
  • Nature. 1993 Feb 4;361(6411):467-70

Degenerin similarities.

Chalfie M, Driscoll M, Huang M.

Publication Types:
  • Comment
  • Letter

PMID: 8429902 [PubMed - indexed for MEDLINE]

29: EMBO J 1992 Dec;11(13):4969-79 Related Articles, Books, Protein, Nucleotide, LinkOut

Regulation of the mec-3 gene by the C.elegans homeoproteins UNC-86 and MEC-3.

Xue D, Finney M, Ruvkun G, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027.

The mec-3 gene encodes a homeodomain protein with LIM repeats that is required for the specification of touch cell fate in Caenorhabditis elegans. Previous experiments suggested that mec-3 expression requires the product of the unc-86 gene, a POU-type homeoprotein, and mec-3 itself. We have analyzed the control of mec-3 expression by identifying potential cis regulatory elements in the mec-3 gene (by conservation in a related nematode and by DNase I footprinting using unc-86 and mec-3 proteins) and testing their importance by transforming C.elegans with mec-3lacZ fusions in which these sites have been mutagenized in vitro. Both unc-86 and mec-3 proteins bind specifically to the promoter of the mec-3 gene, suggesting that both proteins may be directly involved in the regulation of the mec-3 gene. In addition, the footprint pattern with mec-3 protein is altered in the presence of unc-86 protein. In vivo transformation experiments reveal that some of the binding regions of the two proteins are needed for general positive control and maintenance of mec-3 expression while others have no detectable, unique function. Interestingly, the unc-86 gene appears to be required not only to initiate mec-3 expression but also to maintain it.

PMID: 1361171 [PubMed - indexed for MEDLINE]

30: Trends Neurosci 1992 Jan;15(1):15-9 Related Articles, Books

Developmental and abnormal cell death in C. elegans.

Driscoll M, Chalfie M.

Dept of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855.

Genetic analysis in Caenorhabditis elegans has identified several genes that function in normal developmental death as well as genes that can mutate to cause inappropriate cell death. The processes whereby some of these abnormal deaths occur depend on genes that participate in normal programmed cell death; others occur by an independent mechanism whereby mutation of members of a gene family leads to cell lysis. Molecular characterization of these 'death' genes in C. elegans is beginning to provide insight into the normal and aberrant mechanisms of cell death.

Publication Types:
  • Review
  • Review, tutorial

PMID: 1374952 [PubMed - indexed for MEDLINE]

31: Nature 1991 Feb 14;349(6310):588-93 Related Articles, Books, Protein, Nucleotide

Comment in:
  • Nature. 1991 Feb 14;349(6310):564-5

The mec-4 gene is a member of a family of Caenorhabditis elegans genes that can mutate to induce neuronal degeneration.

Driscoll M, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

Three dominant mutations of mec-4, a gene needed for mechanosensation, cause the touch-receptor neurons of Caenorhabditis elegans to degenerate. With deg-1, another C. elegans gene that can mutate to induce neuronal degeneration and that is similar in sequence, mec-4 defines a new gene family. Cross-hybridizing sequences are detectable in other species, raising the possibility that degenerative conditions in other organisms may be caused by mutations in similar genes. All three dominant mec-4 mutations affect the same amino acid. Effects of amino-acid substitutions at this position suggest that steric hindrance may induce the degenerative state.

PMID: 1672038 [PubMed - indexed for MEDLINE]

32: Cell Motil Cytoskeleton 1991;18(3):159-63 Related Articles, Books

Genetic aspects of microtubule biology in the nematode Caenorhabditis elegans.

Savage C, Chalfie M.

Department of Biological Sciences, Columbia University , New York, New York 10027.

Publication Types:
  • Review
  • Review, tutorial

PMID: 2060028 [PubMed - indexed for MEDLINE]

33: Nature 1990 May 31;345(6274):410-6 Related Articles, Books, Protein, Nucleotide

The identification and suppression of inherited neurodegeneration in Caenorhabditis elegans.

Chalfie M, Wolinsky E.

Department of Biological Sciences, Columbia University, New York, New York 10027.

The dominant mutation deg-1(u38) results in a toxic gene product that leads to the late-onset degeneration of a small number of neurons in the nematode Caenorhabditis elegans. Both intragenic and extragenic mutations as well as changes in wild-type gene dosage can delay or block the time of onset of the neuronal deaths. The deg-1 gene has been cloned and a partial complementary DNA reveals that the gene encodes a novel protein that may act as a membrane receptor. Because the late-onset loss of specific sets of neurons, often as a result of dominant mutations, is characteristic of several human neurodegenerative diseases, the analysis of the deg-1 gene and its suppressors may provide a means of understanding the mechanisms underlying some of these human diseases.

PMID: 2342572 [PubMed - indexed for MEDLINE]

34: Neuron 1990 May;4(5):681-95 Related Articles, Books, LinkOut
Click here to read
Organogenesis in C. elegans: positioning of neurons and muscles in the egg-laying system.

Li C, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

One of the final stages in the development of egg-laying behavior in the nematode C. elegans is the organization of 8 motor neurons (2 HSN and 6 VC cells) and 8 muscles into a motor system to control the opening of the vulva. Using mutations that disrupt the development of specific components of the egg-laying system and laser microsurgery to ablate selected precursor cells, we have determined that the guidance of the egg-laying neurons and muscles, and in particular the VC neurons and vulval muscles, into the vulval region is dependent on interactions with surrounding epithelial and gonadal tissue and appears to be independent of neuron-neuron and neuron-muscle interactions. The development of the egg-laying system can be described as a series of cell interactions in which certain cells arise through induction and subsequently provide inductive cues themselves.

PMID: 2344407 [PubMed - indexed for MEDLINE]

35: J Cell Biol 1989 Dec;109(6 Pt 1):2993-3003 Related Articles, Books, Nucleotide

Genetic and molecular analysis of a Caenorhabditis elegans beta-tubulin that conveys benzimidazole sensitivity.

Driscoll M, Dean E, Reilly E, Bergholz E, Chalfie M.

Department of Biological Sciences, Columbia University, New York 10027.

Benzimidazole anti-microtubule drugs, such as benomyl, induce paralysis and slow the growth of the nematode Caenorhabditis elegans. We have identified 28 mutations in C. elegans that confer resistance to benzimidazoles. All resistant mutations map to a single locus, ben-1. Virtually all these mutations are genetically dominant. Molecular cloning and DNA sequence analysis established that ben-1 encodes a beta-tubulin. Some resistant mutants are completely deleted for the ben-1 gene. Since the deletion strains appear to be fully resistant to the drugs, the ben-1 product appears to be the only benzimidazole-sensitive beta-tubulin in C. elegans. Furthermore, since animals lacking ben-1 are viable and coordinated, the ben-1 beta-tubulin appears to be nonessential for growth and movement. The ben-1 function is likely to be redundant in the nematode genome.

PMID: 2592410 [PubMed - indexed for MEDLINE]

36: Curr Opin Cell Biol 1989 Dec;1(6):1122-6 Related Articles, Books

Caenorhabditis elegans development.

Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York.

Publication Types:
  • Review
  • Review literature

PMID: 2576859 [PubMed - indexed for MEDLINE]

37: Genes Dev 1989 Dec;3(12A):1823-33 Related Articles, Books

The mec-3 gene of Caenorhabditis elegans requires its own product for maintained expression and is expressed in three neuronal cell types.

Way JC, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

The homeo-box-containing gene mec-3 of the nematode Caenorhabditis elegans, is expressed in several sensory neurons, as assayed by expression of a mec-3-lacZ fusion. These cells are the touch receptors, which mediate the response to gentle touch, and the FLP and PVD neurons. PVD mediates a response to harsh mechanical stimuli, and FLP has an ultrastructure suggestive of a mechanoreceptor, but its function is unknown. mec-3 is necessary for the differentiation of the touch receptors, because in mec-3 mutants, the touch receptors do not function and have none of their distinguishing features. mec-3 is also needed for PVD function: The PVD neurons no longer mediate a response to harsh mechanical stimuli in the mutants. The expression of the mec-3-lacZ fusion, and presumably mec-3 itself, is altered by mutations in several genes originally identified by their effects on touch cell development. unc-86, another homeo-box-containing gene, is necessary for all mec-3-lacZ expression, but also affects several other lineages and cells in which mec-3 is not expressed. mec-3 activity appears to be required for maintained expression of the mec-3-lacZ fusion in all cells in which it is expressed. In a mec-17 mutant, mec-3-lacZ expression is not maintained in the touch receptors, but is not affected in the FLP and PVD neurons. These findings suggest that combinatorial mechanisms of gene regulation control both the expression of mec-3 itself and its action in promoting the terminal differentiation of various cell types.

PMID: 2576011 [PubMed - indexed for MEDLINE]

38: Genes Dev 1989 Jun;3(6):870-81 Related Articles, Books, Protein, Nucleotide

mec-7 is a beta-tubulin gene required for the production of 15-protofilament microtubules in Caenorhabditis elegans.

Savage C, Hamelin M, Culotti JG, Coulson A, Albertson DG, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

In the nematode Caenorhabditis elegans, microtubules with 15 protofilaments are a specialized feature of six touch-receptor neurons; microtubules found in other C. elegans neurons have 11 protofilaments. Mutations in the gene mec-7 result in touch-insensitive animals whose touch cells lack the 15-protofilament microtubules. We have characterized 54 mutations in the mec-7 gene. The absence of mec-7 activity results selectively in the recessive loss of touch sensitivity. Partial loss-of-function alleles result in a partial loss of touch sensitivity. Dominant mutations, which are isolated at an unusually high proportion, may encode abnormal products. We have cloned the mec-7 gene; it encodes a beta-tubulin which is 90-93% identical to vertebrate beta-tubulin. Our results are consistent with the hypothesis that tubulin heterogeneity contributes to the formation of structurally and functionally distinct sets of microtubules.

PMID: 2744465 [PubMed - indexed for MEDLINE]

39: Science 1989 Feb 24;243(4894 Pt 1):1027-33 Related Articles, Books

Genetic control of differentiation of the Caenorhabditis elegans touch receptor neurons.

Chalfie M, Au M.

Department of Biological Sciences, Columbia University, New York, NY 10027.

The genetic control of neuronal differentiation has been studied by examining mutations that affect the development and function of the six touch receptor neurons of the nematode Caenorhabditis elegans. By screening for touch-insensitive mutants, it has been possible to identify 18 genes (represented by 417 mutations) that are required at various stages in the developmental program for touch cell differentiation. Two of the genes are needed for the generation of precursors in the touch cell lineages; without the precursors, touch cells are not made. A third gene, mec-3, specifies the differentiation of the touch cells, probably by acting as a transcription factor. The remaining 15 genes are likely targets of mec-3 action; mutants defective in these genes have nonfunctioning, yet differentiated, touch cells. Some of these latter genes are needed for the formation of cell-specific components of the touch cells, such as a set of microtubules that are only found in these cells. The study of the touch genes should help us understand how touch cell fate is determined, how microtubule form is specified, and, perhaps, how mechanical stimuli are transduced.

Publication Types:
  • Review
  • Review, tutorial

PMID: 2646709 [PubMed - indexed for MEDLINE]

40: Cell 1988 Jul 1;54(1):5-16 Related Articles, Books, Protein, Nucleotide, OMIM, LinkOut
Click here to read
mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans.

Way JC, Chalfie M.

Department of Biological Sciences, Columbia University, New York, New York 10027.

The mec-3 gene is essential for proper differentiation of the set of six touch receptor neurons in C. elegans. In mutants lacking mec-3 activity, the touch receptors express none of their unique differentiated features and appear to be transformed into other types of neurons. We cloned the mec-3 gene by transposon tagging and showed that a mec-3 mutant can be rescued by germ line transformation using a 5.6 kb genomic DNA fragment. In a strain in which transforming mec-3 DNA is present in about 50 copies per haploid genome, additional cells express a mec-3-dependent phenotype. The putative coding sequence of mec-3 contains a homeobox, suggesting that the mec-3 protein specifies the expression of touch cell differentiation by binding to DNA and regulating transcription of genes that encode the differentiated features of these cells.

PMID: 2898300 [PubMed - indexed for MEDLINE]

41: Trends Neurosci 1988 May;11(5):212-3 Related Articles, Books

Stephen M. Schuetze (1951-1987).

Chalfie M, Siegelbaum SA.

Publication Types:
  • Biography
  • Historical article

Personal Name as Subject:
  • Schuetze SM

PMID: 2471325 [PubMed - indexed for MEDLINE]

42: Science 1988 Feb 5;239(4840):643-5 Related Articles, Books

Cell-cell interactions in the guidance of late-developing neurons in Caenorhabditis elegans.

Walthall WW, Chalfie M.

Department of Biological Sciences, Columbia University, New York, NY 10027.

The initial outgrowth of developing neuronal processes can be affected by a number of extrinsic interactions. Cell-cell interactions are also important in a later stage of neuronal outgrowth when processes grow into the region of their targets. The correct positioning of the process of a postembryonic sensory neuron, the touch cell AVM of the nematode Caenorhabditis elegans, at its synaptic targets requires the presence of a pair of embryonic interneurons, the BDU cells. These cells receive synapses from AVM but do not participate in the touch reflex circuit. Therefore, the AVM-BDU synapses may be required to stabilize the association between these cells and assist in the guidance of the AVM processes through a mature neuropil.

PMID: 3340848 [PubMed - indexed for MEDLINE]

43: J Cell Sci Suppl 1986;5:257-71 Related Articles, Books

Mutations affecting microtubule structure in Caenorhabditis elegans.

Chalfie M, Dean E, Reilly E, Buck K, Thomson JN.

Department of Biological Sciences, Columbia University, New York, NY 10027.

Three types of microtubules are seen in the neuronal processes of the nematode Caenorhabditis elegans. Single cytoplasmic microtubules of most neurones have 11 protofilaments whereas those of six touch receptor cells have 15 protofilaments. The axonemes of sensory cilia have nine outer doublets with a variable number (up to seven) of singlet microtubules. Mutations in 11 genes affect the appearance of these microtubules.

PMID: 3477555 [PubMed - indexed for MEDLINE]

44: J Neurosci 1985 Apr;5(4):956-64 Related Articles, Books

The neural circuit for touch sensitivity in Caenorhabditis elegans.

Chalfie M, Sulston JE, White JG, Southgate E, Thomson JN, Brenner S.

The neural pathways for touch-induced movement in Caenorhabditis elegans contain six touch receptors, five pairs of interneurons, and 69 motor neurons. The synaptic relationships among these cells have been deduced from reconstructions from serial section electron micrographs, and the roles of the cells were assessed by examining the behavior of animals after selective killing of precursors of the cells by laser microsurgery. This analysis revealed that there are two pathways for touch-mediated movement for anterior touch (through the AVD and AVB interneurons) and a single pathway for posterior touch (via the PVC interneurons). The anterior touch circuitry changes in two ways as the animal matures. First, there is the formation of a neural network of touch cells as the three anterior touch cells become coupled by gap junctions. Second, there is the addition of the AVB pathway to the pre-existing AVD pathway. The touch cells also synapse onto many cells that are probably not involved in the generation of movement. Such synapses suggest that stimulation of these receptors may modify a number of behaviors.

PMID: 3981252 [PubMed - indexed for MEDLINE]

45: Science 1983 Jul 1;221(4605):61-3 Related Articles, Books

Induction of neuronal branching in Caenorhabditis elegans.

Chalfie M, Thomson JN, Sulston JE.

The two postembryonic touch receptor neurons in the nematode Caenorhabditis elegans arise from essentially identical cell lineages and have the same ultrastructural features. The cells are found in different positions in the animal, however, and differ in neuronal branching, connectivity, and function. These structural and functional differences are not seen when cells are placed in similar positions by mutation or laser-induced damage. Thus, some, but probably not all, of the differentiated properties of these cells are a consequence of their cellular environment.

PMID: 6857263 [PubMed - indexed for MEDLINE]

46: Science 1982 May 28;216(4549):1012-4 Related Articles, Books

Serotonin and octopamine in the nematode Caenorhabditis elegans.

Horvitz HR, Chalfie M, Trent C, Sulston JE, Evans PD.

The biogenic amines serotonin and octopamine are present in the nematode Caenorhabditis elegans. Serotonin, detected histochemically in whole mounts, is localized in two pharyngeal neurons that appear to be neurosecretory. Octopamine, identified radioenzymatically in crude extracts, probably is also localized in a few neurons. Exogenous serotonin and octopamine elicit specific and opposite behavioral responses in Caenorhabditis elegans, suggesting that these compounds function physiologically as antagonists.

PMID: 6805073 [PubMed - indexed for MEDLINE]

47: J Cell Biol 1982 Apr;93(1):15-23 Related Articles, Books

Structural and functional diversity in the neuronal microtubules of Caenorhabditis elegans.

Chalfie M, Thomson JN.

Tannic acid fixation reveals differences in the number of protofilaments between microtubules (MTs) in the nematode Caenorhabditis elegans. Most cells have MTs with 11 protofilaments but the six touch receptor neurons (the microtubule cells) have MTs with 15 protofilaments. No 13-protofilament (13-p) MT has been seen. The modified cilia of sensory neurons also possess unusual structures. The cilia contain nine outer doublets with A subfibers of 13 protofilaments and B subfibers of 11 protofilaments and a variable number of inner singlet MTs containing 11 protofilaments. The 15-p MTs but not the 11-p MTs are eliminated by colchicine-treatment or by mutation of the gene mec-7. Concomitantly, touch sensitivity is also lost. However, whereas colchicine treatment leads to the loss of all MTs from the microtubule cells, mutations in mec-7 result in the partial replacement of the 15-p MTs with 11-p MTs. Benzimidazoles (benomyl and nocodazole) have more general effects on C. elegans (slow growth, severe uncoordination, and loss of processes from the ventral cord) but do not affect the 15-p MTs. Benomyl will, however, disrupt the replacement 11-p MTs found in the microtubule cells of mec-7 mutants. The 11-p and 15-p MTs also respond differently to temperature and fixation conditions. It is likely that either type of MT will suffice for the proper outgrowth of the microtubule cell process, but only the 15-p MT can function in the specialized role of sensory transduction of the microtubule cells.

PMID: 7068753 [PubMed - indexed for MEDLINE]

48: Cold Spring Harb Symp Quant Biol 1982;46 Pt 1:255-61 Related Articles, Books

Microtubule structure in Caenorhabditis elegans neurons.

Chalfie M.

PMID: 6955083 [PubMed - indexed for MEDLINE]

49: Cell 1981 Apr;24(1):59-69 Related Articles, Books, LinkOut
Click here to read
Mutations that lead to reiterations in the cell lineages of C. elegans.

Chalfie M, Horvitz HR, Sulston JE.

Cells in the nematode Caenorhabditis elegans arise from invariant cell lineages. Mutations in two genes, unc-86 and lin-4, alter multiple and mutually exclusive sets of these lineages. In these mutants, particular cells repeat division patterns normally associated with their parental or grandparental progenitors. The effects of unc-86 are highly specific, altering in equivalent ways the lineages of three post-embryonic neuroblasts that in the wild-type undergo similar division patterns. The effects of lin-4 are more varied, resulting in a number of types of lineage reiterations as well as in supernumerary molts and the continued synthesis of larval-specific cuticle. The reiteration of a given cell division or pattern of cell divisions leads to the repeated generation of cells indistinguishable (by both light and electron microscopy) from those produced after the same division or pattern of cell divisions in the wild-type. This correlation between lineage history and cell fate suggests that in C. elegans a particular sequence of cell divisions may be necessary for the generation of a particular cell type. Reiterative lineages, often referred to as stem cell lineages, may be basic to the development of nematodes and other organisms. We suggest that the wild-type unc-86 and lin-4 genes act to modify latent reiterative cell lineages, which are revealed when the activity of one of these genes is eliminated.

PMID: 7237544 [PubMed - indexed for MEDLINE]

50: Dev Biol 1981 Mar;82(2):358-70 Related Articles, Books

Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans.

Chalfie M, Sulston J.

PMID: 7227647 [PubMed - indexed for MEDLINE]

51: J Cell Biol 1979 Jul;82(1):278-89 Related Articles, Books

Organization of neuronal microtubules in the nematode Caenorhabditis elegans.

Chalfie M, Thomson JN.

We have studied the organization of microtubules in neurons of the nematode Caenorhabditis elegans. Six neurons, which we call the microtubule cells, contain bundles of darkly staining microtubules which can be followed easily in serial-section electron micrographs. Reconstruction of individual microtubules in these cells indicate that most, if not all, microtubules are short compared with the length of the cell process. Average microtubule length varies characteristically with cell type. The arrangement of microtubules gives an overall polarity to each bundle: the distal ends of the microtubles are on the outside of the bundle, whereas the proximal ends are preferentially inside. The distal and proximal ends each have a characteristic appearance indicating that these microtubules may have a polarity of their own. Short microtubules in processes of other neurons in C. elegans have also been observed.

PMID: 479300 [PubMed - indexed for MEDLINE]

52: Mol Pharmacol 1979 Mar;15(2):263-70 Related Articles, Books

The role of cyclic adenosine 3':5'-monophosphate in the regulation of tyrosine 3-monooxygenase activity.

Chalfie M, Settipani L, Perlman RL.

PMID: 38391 [PubMed - indexed for MEDLINE]

53: Biochem Pharmacol 1978 Mar 1;27(5):673-7 Related Articles, Books, LinkOut

Activation of tyrosine 3-mono-oxygenase in pheochromocytoma cells by lasalocid.

Chalfie M, Settipani L, Perlman RL.

PMID: 26348 [PubMed - indexed for MEDLINE]

54: Clin Endocrinol Metab 1977 Nov;6(3):551-76 Related Articles, Books

Catecholamine release from the adrenal medulla.

Perlman RL, Chalfie M.

Chromaffin cells in the adrenal medulla are specialized for the synthesis, storage, and secretion of catecholamines. These cells are innervated by preganglionic sympathetic neurons in the splanchnic nerves, and, because of their unique blood supply, are exposed to unusually high concentrations of glucocorticoids in the venous drainage from the adrenal cortex. Splanchnic nerve stimulation appears to be the most important determinant of adrenomedullary function. Chromaffin cells synthesize catecholamines from tyrosine. Splanchnic nerve stimulation leads to an increase in the activity of several of the catecholamine biosynthetic enzymes, and to an increase in the rate of catecholamine biosynthesis. Glucocorticoids cause the induction of the enzyme noradrenaline N-methyltransferase, and so are particularly important for the synthesis of epinephrine. Catecholamines are stored, together with ATP, Ca2+, and protein, in secretory vesicles known as chromaffin granules. Splanchnic nerve stimulation is the physiological stimulus for catecholamine secretion. Stimulation of the splanchnic nerves results in the release of ACh from nerve endings in the adrenal medulla. ACh causes an increase in the permeability of the chromaffin cells to Ca2+, and thereby leads to the entry of Ca2+ into the cells. Ca2+ then causes the secretion of catecholamines and of other chromaffin granule constituents from the chromaffin cells by exocytosis. The biochemical mechanisms of exocytosis, and the mechanism by which Ca2+ stimulates this process, are still unknown.

Publication Types:
  • Review

PMID: 338214 [PubMed - indexed for MEDLINE]

55: J Neurochem 1977 Oct;29(4):757-9 Related Articles, Books

Inhibition of catecholamine synthesis and tyrosine 3-monooxygenase activation in pheochromocytoma cells by diphenylhydantoin.

Chalfie M, Perlman RL.

PMID: 22586 [PubMed - indexed for MEDLINE]

56: J Pharmacol Exp Ther 1977 Mar;200(3):588-97 Related Articles, Books

Regulation of catecholamine biosynthesis in a transplantable rat pheochromocytoma.

Chalfie M, Perlman RL.

Cells prepared from a transplantable rat pheochromocytoma synthesize norepinephrine from 14C-tyrosine, at a rate of 9.4 +/- 0.5 pml/min/mg of protein, in vitro. Incubation of the cells in a medium containing 56 mM K+ results in a 2- to 6-fold increase in norepinephrine synthesis. This increase in norepinephrine synthesis is dependent upon the presence of Ca++ in the incubation medium. Stimulation of the cells by 56 mM K+ increases the conversion of tyrosine to dopa in the presence of brocresine (an inhibitor of aromatic L-amino acid decarboxylase), and has no effect on the conversion of 3H-dopa to norepinephrine. Cells can be depleted of up to 70% of their catecholamine stores by prior incubation in 56 mM K+. Norepinephrine synthesis in catecholamine-depleted cells incubated under control conditions in only slightly (20-40%) greater than it is in nondepleted cells. However, 56 mM K+ PRODUCES A SIMILAR INCREASE IN NOREPINEPHRINE SYNTHESIS IN DEPLETED CELLS AS IT DOES IN NONDEPLETED CELLS. Inhibition of amine oxidase (flavin containing) by preincubaiton with pargyline does not greatly affect catecholamine synthesis. Incubation of the cells in 56 mMK+ results in an increase in tyrosine 3-monooxygenase activity. These results indicate that the depletion of catecholamine stores plays only a minor role in the increase in norepinephrine synthesis caused by the stimulation of chromaffin cells and suggest that the activation of tyrosine 3-monooxygenase plays a more important role in this phenomenon.

PMID: 15098 [PubMed - indexed for MEDLINE]

57: J Neurochem 1976 Dec;27(6):1405-9 Related Articles, Books

Calcium uptake into rat pheochromocytoma cells.

Chalfie M, Hoadley D, Pastan S, Perlman RL.

PMID: 1003215 [PubMed - indexed for MEDLINE]

58: J Pharmacol Exp Ther 1976 Jun;197(3):615-22 Related Articles, Books

Studies of a transplantable rat pheochromocytoma: biochemical characterization and catecholamine secretion.

Chalfie M, Perlman RL.

The biochemistry and secretory characteristics of a transplantable rat pheochromocytoma have been studied. This tumor possesses the enzyme required for the biosynthesis of norepinephrine from tyrosine, and stores large amounts of norepinephrine (33 +/- 3 nmol/mg of protein). The tumor does not have detectable levels of noradrenalin N-methyltransferase, nor does it contain significant amounts of epinephrine. Approximately two-thirds of the catecholamine content, and one-half of the dopamine beta-monoxygenase activity in the tumor can be isolated in a granule fraction by sedimentation. This granule fraction also contains ATP; the molar ratio of catecholamine to ATP in this granule fraction (5.6 +/- 0.9) is similar to that found in granules prepared from normal adrenal glands. Cell suspensions were prepared by mechanical disruption of the tumor. Incubation of these cell suspensions in media containing 56 mM K+, or the divalant cation ionophores, lasolocid or A23187, leads to the release of catecholamine from these cells. The cells do not secrete catecholamine in response to acetycholine. Catecholamine release induced by 56 mM K+ appears to be by exocytosis, since this release is dependent upon extracellular Ca++, and is accompanied by the release of dopamine beta-monooxygenase, but not of lactate dehydrogenase, from the cells. The mechanism by which the ionophores stimulate catecholamine secretion has not been established.

PMID: 932994 [PubMed - indexed for MEDLINE]

59: Exp Eye Res 1973 May 10;15(5):577-84 Related Articles, Books

Ion pumps in the cornea and their stimulation by epinephrine and cyclic-AMP.

Zadunaisky JA, Lande MA, Chalfie M, Neufeld AH.

PMID: 4351365 [PubMed - indexed for MEDLINE]

60: Invest Ophthalmol 1972 Aug;11(8):644-50 Related Articles, Books

Action of epinephrine and other cyclic AMP-mediated agents on the chloride transport of the frog cornea.

Chalfie M, Neufeld AH, Zadunaisky JA.

PMID: 4339814 [PubMed - indexed for MEDLINE]

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