The genetic make-up of ovarian development and function: the focus on the transcription factor FOXL2.
In a 46 XY individual, the presence of the Y chromosome harboring the testis-determining factor (SRY) triggers testis determination and differentiation. In a 46 XX individual, the absence of SRY and the activation of genes associated with the female pathway lead to ovarian development. The latter process has long been considered as a default pathway. However, recent studies have cast doubts on this dogma. Here, after a brief overview of the main steps of ovarian development, we focus on three genes WNT4, RSPO1 and FOXL2 that are essential for ovarian determination, differentiation and/or maintenance. Special attention is paid to FOXL2 whose mutations are responsible for the blepharophimosis syndrome, often associated with female infertility, and for cancer. We highlight the cooperation of WNT4, RSPO1 and FOXL2 within a regulatory network and the need for further research to better understand their role in defining and maintaining ovarian identity.
Molecular and Cellular Pathologies, Institut Jacques Monod, Paris, France.|UFR Sciences du Vivant, Université Paris Diderot-Paris VII, Paris, France.
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Elzaiat
Molecular and Cellular Pathologies, Institut Jacques Monod, Paris, France.|UFR Sciences du Vivant, Université Paris Diderot-Paris VII, Paris, France.
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Todeschini
Molecular and Cellular Pathologies, Institut Jacques Monod, Paris, France.|UFR Sciences du Vivant, Université Paris Diderot-Paris VII, Paris, France.
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Caburet
Molecular and Cellular Pathologies, Institut Jacques Monod, Paris, France.|UFR Sciences du Vivant, Université Paris Diderot-Paris VII, Paris, France.
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Veitia
D016569:Blepharophimosis / Q000235:genetics / Q000473:pathology; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D007247:Infertility, Female / Q000235:genetics / Q000473:pathology; D008297:Male; D010053:Ovary / Q000254:growth & development* / Q000378:metabolism; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D012868:Skin Abnormalities / Q000235:genetics / Q000473:pathology; D019699:Thrombospondins / Q000235:genetics*; D014564:Urogenital Abnormalities / Q000235:genetics / Q000473:pathology; D060528:Wnt4 Protein / Q000235:genetics*; D000098907:R-Spondins
D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors; D051876:Sex-Determining Region Y Protein; D019699:Thrombospondins; D060528:Wnt4 Protein; C421604:FOXL2 protein, human; C503243:RSPO1 protein, human; D000098907:R-Spondins; C497745:SRY protein, human; C555581:WNT4 protein, human
FOXL2; RSPO1; WNT4; ovary; premature ovarian failure; premature ovarian insufficiency