The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance
By D. Schmidt, C. Ovitt, Katrin Anlag, S. Fehsenfeld, L. Gredsted, Anna-Corina Treier, M. Treier. Development, 2004
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Human Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) type I is an autosomal dominant disorder associated with premature ovarian failure (POF) caused by mutations in FOXL2, a winged-helix/forkhead domain transcription factor. Although it has been shown that FOXL2 is expressed in adult ovaries, its function during folliculogenesis is not known. Here, we show that the murine Foxl2 gene is essential for granulosa cell differentiation and ovary maintenance. In Foxl2lacZ homozygous mutant ovaries granulosa cells do not complete the squamous to cuboidal transition leading to the absence of secondary follicles and oocyte atresia. We further demonstrate that activin-βA and anti-Mullerian inhibiting hormone expression is absent or strongly diminished in Foxl2lacZ homozygous mutant ovaries. Unexpectedly, two weeks after birth most if not all oocytes expressed Gdf9 in Foxl2lacZ homozygous mutant ovaries, indicating that nearly all primordial follicles have already initiated folliculogenesis at this stage. This activation, in the absence of functional granulosa cells, leads to oocyte atresia and progressive follicular depletion. In addition to providing a molecular mechanism for premature ovarian failure in BPES, these results suggest that granulosa cell function is not only crucial for oocyte growth but also to maintain follicular quiescence in vivo.
Subfields: Genetics, Molecular Biology, Public Health, Environmental and Occupational Health
View Paper: https://www.semanticscholar.org/paper/82c9c8bab7e7286381e09006b4f7a3c00d69006c
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Citations in the corpus
- The mammalian ovary from genesis to revelation. (2009, background): “Similar to observations in Foxl2-deficient ovaries (187, 188), Ngfdeficient ovaries have reduced somatic cell proliferation, suggesting that NGF signaling is also important in the differentiation of squamous pre-granulosa cells to cuboidal granulosa cells during primordial follicle activation.”
- Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. (2009, background): “5 (Ottolenghi et al., 2005; Schmidt et al., 2004).”
- Sex determination and gonadal development in mammals. (2007, background): “5 dpc, and this expression pattern is conserved between different phyla (139, 207).”