Wnt9b Plays a Central Role in the Regulation of Mesenchymal to Epithelial Transitions Underlying Organogenesis of the Mammalian Urogenital System

Abstract

The vertebrate urogenital system forms due to inductive interactions between the Wolffian duct, its derivative the ureteric bud, and their adjacent mesenchymes. These establish epithelial primordia within the mesonephric (embryonic) and metanephric (adult) kidneys and the Müllerian duct, the anlage of much of the female reproductive tract. We show that Wnt9b is expressed in the inductive epithelia and is essential for the development of mesonephric and metanephric tubules and caudal extension of the Müllerian duct. Wnt9b is required for the earliest inductive response in metanephric mesenchyme. Further, Wnt9b-expressing cells can functionally substitute for the ureteric bud in these interactions. Wnt9b acts upstream of another Wnt, Wnt4, in this process, and our data implicate canonical Wnt signaling as one of the major pathways in the organization of the mammalian urogenital system. Together these findings suggest that Wnt9b is a common organizing signal regulating diverse components of the mammalian urogenital system.

Molecular regulation of kidney development: is the answer blowing in the Wnt?

“…Wnt7b is weakly expressed in the Wolffian duct and the stalk of the UB but not in the vertical portion or tips of the bud at E 11.5 and E 12.5 ( Fig. 3b and f) [42]. At later stages, Wnt7b is expressed in the ureter and distal collecting duct system ( Fig.…”

“…Both Wnt6 and 9b are expressed throughout the Wolffian ducts and the ureteric bud/ proximal collecting duct system from E 10.5 through birth, although expression levels are lower in the ampullary tips (Fig. 3c,g,k,o and [42,43]). Wnt7b is weakly expressed in the Wolffian duct and the stalk of the UB but not in the vertical portion or tips of the bud at E 11.5 and E 12.5 ( Fig.…”

“…Analysis of mouse embryos by in situ hybridization has revealed the expression of six Wnts in the developing kidney: Wnt2b, Wnt4, Wnt6, Wnt7b, Wnt9b, and Wnt11 [9,[42][43][44][45]. Another eight Wnts have been shown to be present by sequencing of urogenital system cDNAs, with only Wnt5b identified as being specifically located in the kidney.…”

“…To test the sufficiency of each of these factors to induce tubules, cells expressing the individual ligands were co-cultured with isolated E 11.0 metanephric mesenchyme. Wnt6, Wnt7b and Wnt9b can all induce tubulogenesis, while Wnt11 cannot [7,42]. Of the "inducing" ureteric bud-expressed ligands, in subsequent genetic studies, only Wnt9b was supported for a role in tubule induction.…”

Genetic association between PAX2 and mullerian duct anomalies in Han Chinese females

“…In recent works, scholars identified that the Pax2 transactivation domain is phosphorylated by the c-Jun N-terminal kinase (JNK) [29]. Research proves that the JNK can regulate downstream of the WNT signaling pathway, which is essential for the development of female reproductive ducts [30]. Other MDA candidate genes, such as LHX1, which also encodes for a transcription factor, participate in the period of mullerian duct formation [31].…”