Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis.
Wnt4(-/-) XX gonads display features normally associated with testis differentiation, suggesting that WNT4 actively represses elements of the male pathway during ovarian development. Here, we show that follistatin (Fst), which encodes a TGFbeta superfamily binding protein, is a downstream component of Wnt4 signaling. Fst inhibits formation of the XY-specific coelomic vessel in XX gonads. In addition, germ cells in the ovarian cortex are almost completely lost in both Wnt4 and Fst null gonads before birth. Thus, we propose that WNT4 acts through FST to regulate vascular boundaries and maintain germ cell survival in the ovary.
Yao
Humphrey H C
HH
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina, USA.
Matzuk
Martin M
MM
Jorgez
Carolina J
CJ
Menke
Douglas B
DB
Page
David C
DC
Swain
Amanda
A
Capel
Blanche
B
D000818:Animals; D017209:Apoptosis; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D038681:Follistatin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D038081:Organogenesis; D010053:Ovary / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D060528:Wnt4 Protein
C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse