C2006/F2402 '08 OUTLINE OF LECTURE #20
Dr. Alice Heicklen, Columbia University, New York, NY
Handouts: 20 A (morphogenesis of gonads and internal tubes), 20B (peritoneal sexual dimorphism, external male genitalia and overall summary)
Outline - Mammalian Sex Determination Decisions
2. Internal Ducts
3. External Genitalia
Last Tuesday we spent a lot of time discussing cell fate determination
We discussed that a major component in this process of cell fate determination is controlled by the transcription factors (TFs) that are turned on in a specific cell. The TFs or master regulatory genes (MRG) determine the proteins that will be expressed in a specific cell, therefore determining cell type.
Today we are going to look at sex determination as an example of cell fate determination.
Four tissues have their cell fate determined by a cascade of events:
The sex of the gonad (somatic tissue) is determined by the presence or the lack of the Y chromosome. The sex of the gonad then determines:
From disruptions or mutations of genes involved in this cascade we can see that there are three decisions or molecular processes that must proceed properly for all of these organs to become the same sex. If any on of these decisions or cascades does not proceed correctly the individual will have some organs or tissues that are male and some organs or tissues that are female = pseudohermaphrodite. Hermaphrodite = gonad has regions that have the somatic tissues of the ovary and regions that have the somatic tissue of the testes.
II. Gonad = primary sex determination (20A top)
The first decision that needs to be made is by the gonad. The cell fate of the gonad in mammals is determined by the sex chromosomes: XX = female and XY = male.
Sry = master regulatory gene for Testes, on Y chromosome, turns on other genes necessary to create somatic tissue of testes – such as TFs (Sox9, SF1), hormones and signaling molecules (Fgf9, enzymes for testosterone production and AMH) – either directly or indirectly
Wnt4 = on in bipotential gonad, on autosomal chromosome, turns on Dax1, Sry inhibits Wnt4, stays on in XX individuals.
Dax1 = master regulatory gene for ovary, on X chromosome, turns on genes necessary to create somatic tissues of the ovary – such as TAFII 150 (protein that works with RNA polymerase II -necessary for ovary development).
Secondary Sex Determination = internal ducts + external genitalia
A. Internal Ducts (20A bottom)
B. External Genitalia
Summary of all components of sex determination (20B bottom)
Sex Determination Disruption
Secondary Sex Disruption: