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Ovary |
a Children's Hospital and Program for Developmental and Reproductive Biology, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland
b The Folkhälsan Institute of Genetics and Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, 00290 Helsinki, Finland
c Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri 63110
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.
2 Correspondence: Markku Heikinheimo, Program for Developmental and Reproductive Biology, Biomedicum Helsinki, Room B525b, P.O. Box 63 (Haartmaninkatu 8), 00014 University of Helsinki, Finland. FAX: 358 9 4717 1947; markku.heikinheimo{at}helsinki.fi
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