title: FOG-2 and GATA-4 Are coexpressed in the mouse ovary and can modulate mullerian-inhibiting substance expression.
abstract: Transcription factor GATA-4 has been suggested to have a role in mammalian gonadogenesis, e.g., through activation of the Müllerian-inhibiting substance (MIS) gene expression. Although the expression of GATA-4 during gonadogenesis has been elucidated in detail, very little is known about FOG-2, an essential cofactor for GATA-4, in ovarian development. We explored in detail the expression of FOG-2 and GATA-4 in the fetal and postnatal mouse ovary and in the fetal testis using Northern blotting, RNA in situ hybridization, and immunohistochemistry. GATA-4 and FOG-2 are evident in the bipotential urogenital ridge, and their expression persists in the fetal mouse ovary; this result is different from earlier reports of GATA-4 downregulation in the fetal ovary. In contrast to ovary, FOG-2 expression is lost in the fetal Sertoli cells along with the formation of the testicular cords, leading to the hypothesis that FOG-2 has a specific role in the fetal ovaries counteracting the transactivation of the MIS gene by GATA-4. In vitro transfection assays verified that FOG-2 is able to repress the effect of GATA-4 on MIS transactivation in granulosa cells. In postnatal ovary, granulosa cells of growing follicles express FOG-2, partially overlapping with the expression of MIS. These data suggest an important role for FOG-2 and the GATA transcription factors in the developing ovary.
authors.affiliation: Children's Hospital and Program for Developmental and Reproductive Biology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Anttonen
authors.forename: Ilkka
authors.initials: I
authors.lastname: Ketola
authors.forename: Helka
authors.initials: H
authors.lastname: Parviainen
authors.forename: Anna-Kaisa
authors.initials: AK
authors.lastname: Pusa
authors.forename: Markku
authors.initials: M
authors.lastname: Heikinheimo
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D054304:Anti-Mullerian Hormone; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D005333:Fetus / Q000378:metabolism; D050991:GATA4 Transcription Factor; D005835:Genitalia / Q000196:embryology / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D010053:Ovary / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013735:Testicular Hormones / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D006023:Glycoproteins; D012333:RNA, Messenger; D013735:Testicular Hormones; D014157:Transcription Factors; C492170:Zfpm2 protein, mouse; D054304:Anti-Mullerian Hormone