title: The transcription factor FOXL2: at the crossroads of ovarian physiology and pathology.
abstract: FOXL2 is a gene encoding a forkhead transcription factor. Its mutations or misregulation have been shown to cause the blepharophimosis-ptosis-epicanthus inversus (BPES) syndrome and more recently have been associated with the development of Ovarian Granulosa Cell Tumors (OGCT). BPES is a genetic disorder involving mild craniofacial abnormalities often associated with premature ovarian failure. OGCTs are endocrine malignancies, accounting for 2-5% of ovarian cancers, the treatment of which is still challenging. In this review we summarize recent data concerning FOXL2 transcriptional targets and molecular partners, its post-translational modifications, its mutations and its involvement in newly discovered pathophysiological processes. In the ovary, FOXL2 is involved in the regulation of cholesterol and steroid metabolism, apoptosis, reactive oxygen species detoxification and cell proliferation. Interestingly, one of the main roles of FOXL2 is also to preserve the identity of ovarian granulosa cells even at the adult stage and to prevent their transdifferentiation into Sertoli-like cells. All these recent advances indicate that FOXL2 is central to ovarian development and maintenance. The elucidation of the impact of FOXL2 germinal and somatic mutations will allow a better understanding of the pathogenesis of BPES and of OGCTs.
authors.affiliation: CNRS UMR 7592, Institut Jacques Monod, Equipe Génétique et Génomique du Développement Gonadique, 75205 Paris Cedex 13, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caburet
authors.forename: Adrien
authors.initials: A
authors.lastname: Georges
authors.forename: David
authors.initials: D
authors.lastname: L'Hôte
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Todeschini
authors.forename: Bérénice A
authors.initials: BA
authors.lastname: Benayoun
authors.forename: Reiner A
authors.initials: RA
authors.lastname: Veitia
mesh_terms: D000818:Animals; D016569:Blepharophimosis / Q000235:genetics; D005260:Female; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008594:Menopause, Premature / Q000235:genetics; D009154:Mutation; D010053:Ovary / Q000378:metabolism / Q000503:physiopathology*; D011499:Protein Processing, Post-Translational; D012868:Skin Abnormalities / Q000235:genetics
chemical_list: C421604:FOXL2 protein, human; D000074842:Forkhead Box Protein L2; D051858:Forkhead Transcription Factors