What is sex determination?
- The earliest developmental event that establishes sex (male or female development)
- Results in differentiation of embryonic gonads into either testes or ovaries
- If testosterone is made by the testes male genitalia will form (female is default)
What is the origin of embryonic gonads?
- The intermediate mesoderm which gives rise to the kidneys and the embryonic gonads which develop on the surface of the embryonic kidney (mesonephros)
What are the homologous female gonad cell types for these males cells:
- Sertoli cells
- Leydig cells
- Granulosa cells (supporting cells)
2. Theca cells (interstitial steroid hormone producing cells)
What is the first cell type to differentiate in the developing testis?
Sertoli cell
What is the critical testis determining factor?
- The TDF is the SRY (sex determining region of the Y) gene carried on the Y chromosome. Its presence in the genotype causes testis development.
- The SRY gene encodes a transcription factor with a DNA binding domain called the HMG box.
What other gene does SRY activate?
- SRY activates SOX9
What are SOX9 genes?
- Encodes a transcriptional activator
- Activated by the SRY gene
- A pleiotropic gene: has more than one function; required for testicular development and for chondrogenesis
- SOX 9 negatively feedacs to SRY; in SOX9 null mice SRY expression is maintained
How does SOX9 lead to testis development?
- It activates male specific genes during testis development such as FGF9
What is the male gonadal activation factor pathway:
- SRY gene present in genome –> activation of SOX9 –> SOX 9 negatively inhibits SRY action –> SOX9 activates FGF9 and other male pathway genes –> FGF9 positively feedbacks to SOX9
Is there a master gene on the X chromosome governing ovary development the same way SRY on the Y chromosome governs testis development?
- No; there are 2 key autosomal genes instead: R-spondin-1 and Wnt4
How do R-SPO1 and Wnt4 cause ovary development?
- R-SPO1 stabilised the beta-catenin pathway (activated by Wnt -> LRP + Fz receptor). RSPO-1 is only expressed in female embryonic gonads and induces Wnt4 expression.
- Wnt4 also upregulates the beta-catenin pathway.
- Wnt4 suppresses the male gonadal pathway
Which are the corresponding antagonistic female gonadal development signals for these male gonadal signals:
1. Sox9 and FGF9
- R-SPO1 and Wnt4
