FOG-2 and GATA-4 Are Coexpressed in the Mouse Ovary and Can Modulate Müllerian-Inhibiting Substance Expression1

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.

GATA‐4:FOG interactions regulate gastric epithelial development in the mouse

“…FOG-1 expression has been documented in hematopoietic progenitors, gonadal cells, and the heart (Tsang et al, 1997;Tevosian et al, 2002;Katz et al, 2003;Gitler et al, 2003), while FOG-2 has been detected in brain, gonadal somatic cells, and cardiac tissue (Tsang et al, 1997(Tsang et al, , 1998Svensson et al, 1999;Tevosian et al, 1999;Lu et al, 1999;Anttonen et al, 2003). However, little is known about FOG-1 or FOG-2 expression in endoderm derivatives.…”

WNT4 is expressed in human fetal and adult ovaries and its signaling contributes to ovarian cell survival

“…For instance, TRAIL, a tumor necrosis factor-related apoptosis-inducing ligand, has been shown to participate in the regulation of apoptosis in mammalian ovaries (Inoue et al 2003, Jaaskelainen et al 2009). Moreover, several transcriptional factors such as GATA-4 and its co-factor FOG-2 participate in the regulation of oocyte survival in mice and men (Heikinheimo et al 1997, Vaskivuo et al 2001, Anttonen et al 2003.…”

An alternative transcript of the FOG-2 gene encodes a FOG-2 isoform lacking the FOG repression motif

“…This interaction is mediated by multiple zinc fingers of the FOG proteins and the N-terminal zinc finger of the GATA factors [9][10][11][12][13]. In most cell and promoter contexts examined to date, this interaction results in the repression of GATA-mediated transactivation of target promoters [14][15][16][17][18][19]. There are two potential domains of FOG proteins that may mediate transcriptional repression.…”