wnt4β-catenin pathway maintains female germ cell survival by inhibiting activin βb in the mouse fetal ovarywnt4β-catenin通路保持女性生殖细胞生存通过抑制苯丙酸诺龙βb胎儿卵巢的老鼠.pdfVIP

WNT4/b-Catenin Pathway Maintains Female Germ Cell Survival by Inhibiting Activin bB in the Mouse Fetal Ovary 1 2 1 Chia-Feng Liu , Keith Parker , Humphrey H.-C. Yao * 1 Department of Veterinary Biosciences, University of Illinois, Urbana-Champaign, Illinois, United States of America, 2 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America Abstract Female germ cells are essential for organogenesis of the ovary; without them, ovarian follicles do not form and functional and structural characteristics of the ovary are lost. We and others showed previously that when either Wnt4 or b-catenin was inactivated in the fetal ovary, female germ cells underwent degeneration. In this study, we set out to understand whether these two factors belong to the same pathway and how they maintain female germ cell survival. We found that activation of b-catenin in somatic cells in the Wnt4 knockout ovary restored germ cell numbers, placing b-catenin downstream of WNT4. In the absence of Wnt4 or b-catenin, female germ cells entered meiosis properly; however, they underwent apoptosis afterwards. Activin bB (Inhbb), a subunit of activins, was upregulated in the Wnt4 and b-catenin knockout ovaries, suggesting that Inhbb could be the cause for the loss of female germ cells, which are positive for activin receptors. Indeed, removal of Inhbb in the Wnt4 knockout ovaries prevented female germ cells from undergoing degeneration. We conclude that WNT4 maintains female germ cell survival by inhibiting Inhbb expression via b-catenin in the somatic cells. Maintenance of female germ cells hinge upon a delicate balance between positive (WNT4 and b-catenin) and negative (activin bB) regulators derived from