Home Page for Jim Erickson's Lab

James Erickson

Columbia University
Biological Sciences
614A Fairchild Center, M.C. 2406
New York, N.Y. 10027
212-854-4625
jwe7@columbia.edu

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Alternative developmental fates are often determined by small differences in the concentrations of signaling molecules. In many cases, cells respond to these signals within narrowly defined temporal windows and are unresponsive to the same signal molecules at other times in development. A number of aspects of Drosophilasex determination make it an ideal experimental system to study how strict temporal controls and small quantitative differences in protein concentration can elicit different developmental fates.

Sex is determined in Drosophilaby the number of X chromosomes, with one X specifying male development and two specifying female. The dose of X chromosomes controls sex determination through its effects on the establishment promoter, SxlPe, of the regulatory gene Sex-lethal. Female development occurs as a consequence of Sxl being turned on in diplo-X animals while male development occurs in haplo-X animals because Sxl is left inactive. Although Sxl protein is required at all times to direct female differentiation, X chromosome dose affects Sxl expression only during a 30-40 min period in the pre-cellular embryo. After this time, Pe shuts off and Sxl is transcribed from a maintenance promoter, Pm, that is insensitive to X chromosome dose.

Genetic experiments have identified five elements on the X chromosome whose relative dose (one vs. two) is used to determine sex. These include the genes sisterlessA and -B, -C, runt, as well as Sxl itself. The sisA sisB and runt genes encode transcriptional activators of the bZIP, bHLH, and runt/AML class. The dose of these "counted" elements is measured with respect to a number of maternal and zygotically expressed proteins, some of which function as activators and some as inhibitors. We are studying the molecular interactions between the positively acting and inhibitory protein factors and their SxlPe promoter target. Our approach combines biochemistry with classical and molecular genetic analyses to identify novel molecules, and to characterize the protein/protein and protein/DNA interactions that regulate SxlPe. Given the ability to identify the key regulatory molecules, to study their expression, and to manipulate their levels and activity, in vitro, and in vivo; studies on Drosophila sex determination should prove ideal for understanding how transcriptional regulators of different classes can cooperate to generate sharp threshold responses.



Representative Publications

Erickson, J.W. (in preparation). Is the X/A ratio the Drosophila sex determination signal? Haploid embryos are mosaics for Sex-lethal activation.

Erickson, J.W. (2001) Sex and Neighboring Cell. Developmental Cell 1:156-158.

Yang D., H. Lu, Y. Hong, T.M. Jinks, P.A. Estes, and J.W. Erickson. (2001) Interpretation of X chromosome dose at Sex-lethal requires non-E-box sites for the bHLH proteins SISB and Daughterless. Mol. Cell. Biol. 21:1581-1592.

Yang, D., H. Lu and J.W. Erickson (2000). Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Current Biology 10:1191-1200.

Walker, J.J., K. K. Lee, R. N. Desai, and J.W. Erickson (2000). The Drosophila melanogaster sex determination gene sisA is required in yolk nuclei for midgut formation. GENETICS 155: 191-202.

Erickson, J.W. and T.W. Cline (1998). Key Aspects of the Primary Sex Determination Mechanism are Conserved Across the Genus Drosophila. Development 125: 3259-3268.

Erickson, J.W. and T.W. Cline (1993). A bZIP protein, SISTERLESS-A, collaborates with bHLH transcription factors early in Drosophila development to determine sex. Genes & Devel. 7:1688-1702.Abstract

Erickson, J.W. and T.W. Cline (1991). Molecular nature of the Drosophila sex determination signal and its link to neurogenesis. Science 251:1071-1074.Abstract

Courses Taught:

Course Number

Title

W3031

Genetics

Lab Members

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