Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimullerian hormone expression during oocyte maturation in the female follicle. Issue 4 (26th December 2013)

• Record Type: Journal Article
• Authors: Prunskaite‐Hyyrylainen, Renata; Shan, Jingdong; Railo, Antti; Heinonen, Krista M.; Miinalainen, Ilkka; Yan, Wenying; Shen, Bairong; Perreault, Claude; Vainio, Seppo J.
• Is Part Of: FASEB journal. Volume 28:Issue 4(2014)
• Page Start: 1568
• Page End: 1581
• Publication Date: 2013-12-26
• Subjects: sex determination -- cell polarity -- ovarian development -- premature ovarian failure; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.13-233247
• Languages: English
• ISSNs: 0892-6638

Abstract

Abstract : Wnt4 is a key signal that channels the developmental fate of the indifferent mammalian gonad toward the ovary, but whether Wnt4 has later roles during ovary development remains unknown. To investigate this, we inactivated the Wnt4 gene by crossing Amhr2Cre and doxycycline‐inducible Rosa rtTA ‐knock‐in Cre mice with mice carrying a floxed Wnt4 allele and used a novel Wnt4 mCherry ‐knock‐in mouse. In these models, ovarian folliculogenesis was compromised, and female fertility was severely reduced, and Wnt4 deficiency eventually led to premature ovarian failure. These anomalies were associated with cell polarity defects in the follicle. Within the follicle, laminin and type IV collagen assembled ectopic basement membrane–like structures, the cell adherens junction components N‐cadherin and β‐catenin lost their polarized expression pattern, and expression of the gap junction protein connexin 43 was reduced by ~30% when compared with that of the controls. Besides these changes, expression of antimullerian hormone ( Amh ) was inhibited in the absence of Wnt4 signaling in vivo . Consistent with this, Wnt4 signaling up‐regulated Amh gene expression in KK1 cells in vitro . Thus, Wnt4 signaling is necessary during maturation of the ovarian follicles, where it coordinates expression of Amh, cell survival, and polarized organization of the follicular cells.—Prunskaite‐Hyyrylainen, R., Shan, J., Railo, A., Heinonen, K. M., Miinalainen, I., Yan, W., Shen, B., Perreault, C., Vainio, S.J. Wnt4, a pleiotropic signal for controlling cell polarity, basement membrane integrity, and antimullerian hormone expression during oocyte maturation in the female follicle. FASEB J. 28, 28–1568 (1581). www.fasebj.org