FOXL2 and BMP2 act cooperatively to regulate Follistatin gene expression during ovarian development

Kashimada, Kenichi, Pelosi, Emanuele, Chen, Huijun, Schlessinger, David, Wilhelm, Dagmar and Koopman, Peter (2011) FOXL2 and BMP2 act cooperatively to regulate Follistatin gene expression during ovarian development. Endocrinology, 152 1: 272-280. doi:10.1210/en.2010-0636


Author Kashimada, Kenichi
Pelosi, Emanuele
Chen, Huijun
Schlessinger, David
Wilhelm, Dagmar
Koopman, Peter
Title FOXL2 and BMP2 act cooperatively to regulate Follistatin gene expression during ovarian development
Formatted title
FOXL2 and BMP2 act cooperatively to regulate Follistatin gene expression during ovarian development
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
2150-5810
Publication date 2011-01-01
Year available 2010
Sub-type Article (original research)
DOI 10.1210/en.2010-0636
Open Access Status Not yet assessed
Volume 152
Issue 1
Start page 272
End page 280
Total pages 9
Place of publication London, U.K.
Publisher Portland Press
Language eng
Subject 1310 Endocrinology
Abstract Follistatin is a secreted glycoprotein required for female sex determination and early ovarian development, but the precise mechanisms regulating follistatin (Fst) gene expression are not known. Here, we investigate the roles of bone morphogenetic protein 2 (BMP2) and forkhead-domain transcription factor L2 (FOXL2) in the regulation of Fst expression in the developing mouse ovary. Bmp2 and Fst showed similar temporal profiles of mRNA expression, whereas FOXL2 protein and Fst mRNA were coexpressed in the same ovarian cells. In a cell culture model, both FOXL2 and BMP2 up-regulated Fst expression. In ex vivo mouse fetal gonad culture, exogenous BMP2 increased Fst expression, but this effect was counteracted by the BMP antagonist Noggin. Moreover, in Foxl2-null mice, Fst expression was reduced throughout fetal ovarian development, and Bmp2 expression was also reduced. Our data support a model in which FOXL2 and BMP2 cooperate to ensure correct expression of Fst in the developing ovary. Further, Wnt4-knockout mice showed reduced expression of Fst limited to early ovarian development, suggesting a role for WNT4 in the initiation, but not the maintenance, of Fst expression. (Endocrinology 152: 272-280, 2011)
Formatted abstract
Follistatin is a secreted glycoprotein required for female sex determination and early ovarian development, but the precise mechanisms regulating follistatin (Fst) gene expression are not known. Here, we investigate the roles of bone morphogenetic protein 2 (BMP2) and forkheaddomain transcription factor L2 (FOXL2) in the regulation of Fst expression in the developing mouse ovary. Bmp2 and Fst showed similar temporal profiles ofmRNAexpression, whereas FOXL2 protein and Fst mRNA were coexpressed in the same ovarian cells. In a cell culture model, both FOXL2 and BMP2 up-regulated Fst expression. In ex vivo mouse fetal gonad culture, exogenous BMP2 increased Fst expression, but this effect was counteracted by the BMP antagonist Noggin. Moreover, in Foxl2-null mice, Fst expression was reduced throughout fetal ovarian development, and Bmp2 expression was also reduced. Our data support a model in which FOXL2 and BMP2 cooperate to ensure correct expression of Fst in the developing ovary. Further, Wnt4-knockout mice showed reduced expression of Fst limited to early ovarian development, suggesting a role for WNT4 in the initiation, but not the maintenance, of Fst expression. Copyright
© 2010 The Endocrine Society. All rights reserved.
Keyword Transcription factor Foxl2
Granulosa-cell lines
Sex determination
Mice deficient
Female
Differentiation
Defects
Wnt4
Deletion
Activin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Originally published online Nov 17, 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Sun, 30 Jan 2011, 10:06:05 EST