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Opposing gene signals (differential activation) determines fate of primordial gonad as a testis or ovary. RSPO1, respondin 1; WNT4, human homolog of
Drosophila wingless gene; FOXL-2, forkhead box L2; β-catenin, key-regulated effector of the WNT-signaling pathway. DAX-1 (DSS-AHC-critical region on
the X chromosome gene 1) RSPO1 activates the WNT4/β-catenin canonical-signaling pathway which inhibits SOX9 expression and promotes ovarian
differentiation. SRY upregulates SOX9 by binding to testicular enhancing elements in the SOX9 gene (TESCO), and both SRY and SOX9 (in mice) inhibit
the β-catenin canonical-signaling pathway and promote Sertoli cell and consequent testicular development. A feed-forward loop involving SF-1 and FGF-9
has been demonstrated in mice which maintains SOX9 expression. FOXL2 "knockout" in mice causes gonadal sex reversal, i.e., ovary to testes
Source: Chapter 14. Disorders of Sex Determination and Differentiation, Greenspan’s Basic & Clinical Endocrinology, 9e
suggesting that FOXL2 inhibits SOX9 expression. No human homozygous FOXL2 null mutations have been reported as yet. Duplication of DAX1 or WNT4
Citation:of
Gardner
DG,development
Shoback D. Greenspan’s
& Clinical Endocrinology,
9e; 2011
Available
at: http://mhmedical.com/
Accessed:
August
results in inhibition
testicular
and atypicalBasic
genitalia—dysgenetic
46,XY DSD.
MAP3K4,
mitogen-activated
protein kinase
4; CBX2,
03,
2017
chromobox homologue 2. It has been suggested that CBX2 is upstream of SRY. More complete understanding of the exact function of MAP3K4 remains to
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be elucidated.