Topic E4

Question 1

What is sex determination?

Answer 1

• 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)

Question 2

What is the origin of embryonic gonads?

Answer 2

• The intermediate mesoderm which gives rise to the kidneys and the embryonic gonads which develop on the surface of the embryonic kidney (mesonephros)

Question 3

What are the homologous female gonad cell types for these males cells:

1. Sertoli cells
2. Leydig cells

Answer 3

1. Granulosa cells (supporting cells)

2. Theca cells (interstitial steroid hormone producing cells)

Question 4

What is the first cell type to differentiate in the developing testis?

Answer 4

Sertoli cell

Question 5

What is the critical testis determining factor?

Answer 5

• 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.

Question 6

What other gene does SRY activate?

Answer 6

• SRY activates SOX9

Question 7

What are SOX9 genes?

Answer 7

• 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

Question 8

How does SOX9 lead to testis development?

Answer 8

• It activates male specific genes during testis development such as FGF9

Question 9

What is the male gonadal activation factor pathway:

Answer 9

• 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

Question 10

Is there a master gene on the X chromosome governing ovary development the same way SRY on the Y chromosome governs testis development?

Answer 10

• No; there are 2 key autosomal genes instead: R-spondin-1 and Wnt4

Question 11

How do R-SPO1 and Wnt4 cause ovary development?

Answer 11

• 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

Question 12

Which are the corresponding antagonistic female gonadal development signals for these male gonadal signals:
1. Sox9 and FGF9

Answer 12

1. R-SPO1 and Wnt4