Wnt5a regulates intermediate mesoderm extension and kidney morphogenesis

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NCI	DEV-13

Authors

• N Sharma
• R Ajima
• T.P. Yamaguchi
• A.O. Perantoni

Abstract

Duplex kidney formation is a relatively common congenital abnormality affecting about 1% of the population, but the basis for this defect is ill understood. While investigating the role of Wnt5a in metanephric development, we found that its specific inactivation in mesoderm results in bilateral duplex kidney formation. Wnt5a is expressed in a gradient manner at both the cranial and caudal ends of the IM before ureteric bud outgrowth, but not at the time of ureteric bud outgrowth. Thus, double ureters form only in the Wnt5a mutants using Cre lines which eliminate Wnt5a expression in the posterior IM, but not in Wnt5a mutants without its deletion in the posterior IM although they are active within the kidney itself. Moreover, Wnt5a mutation induced before IM formation yielded Wnt5a-deficient embryos with double ureters; whereas its induction during IM formation resulted in mutants with normal IM extension and single ureters. The nephric duct bifurcates at its caudal terminus of mutant embryos before ureteric bud outgrowth, thus forming twin epithelial UB outgrowths in the surrounding MM. These results suggest that Wnt5a regulates IM extension and that its loss in the IM causes duplex kidney formation.

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