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Publication : CTNNB1 in mesenchyme regulates epithelial cell differentiation during Müllerian duct and postnatal uterine development.

First Author  Stewart CA Year  2013
Journal  Mol Endocrinol Volume  27
Issue  9 Pages  1442-54
PubMed ID  23904126 Mgi Jnum  J:314892
Mgi Id  MGI:6822519 Doi  10.1210/me.2012-1126
Citation  Stewart CA, et al. (2013) CTNNB1 in mesenchyme regulates epithelial cell differentiation during Mullerian duct and postnatal uterine development. Mol Endocrinol 27(9):1442-54
abstractText  Mullerian duct differentiation and development into the female reproductive tract is essential for fertility, but mechanisms regulating these processes are poorly understood. WNT signaling is critical for proper development of the female reproductive tract as evident by the phenotypes of Wnt4, Wnt5a, Wnt7a, and beta-catenin (Ctnnb1) mutant mice. Here we extend these findings by determining the effects of constitutive CTNNB1 activation within the mesenchyme of the developing Mullerian duct and its differentiated derivatives. This was accomplished by crossing Amhr2-Cre knock-in mice with Ctnnb1 exon (ex) 3(f/f) mice. Amhr2-Cre(Delta/+); Ctnnb1 ex3(f/+) females did not form an oviduct, had smaller uteri, endometrial gland defects, and were infertile. At the cellular level, stabilization of CTNNB1 in the mesenchyme caused alterations within the epithelium, including less proliferation, delayed uterine gland formation, and induction of an epithelial-mesenchymal transition (EMT) event. This EMT event is observed before birth and is complete within 5 days after birth. Misexpression of estrogen receptor alpha in the epithelia correlated with the EMT before birth, but not after. These studies indicate that regulated CTNNB1 in mesenchyme is important for epithelial cell differentiation during female reproductive tract development.
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