Requirement of Wnt/β-catenin signaling in pronephric kidney development

Abstract

The pronephric kidney controls water and electrolyte balance during early fish and amphibian embryogenesis. Many Wnt signaling components have been implicated in kidney development. Specifically, in Xenopus pronephric development as well as the murine metanephroi, the secreted glycoprotein Wnt-4 has been shown to be essential for renal tubule formation. Despite the importance of Wnt signals in kidney organogenesis, little is known of the definitive downstream signaling pathway(s) that mediate their effects. Here we report that inhibition of Wnt/β-catenin signaling within the pronephric field of Xenopus results in significant losses to kidney epithelial tubulogenesis with little or no effect on adjoining axis or somite development. We find that the requirement for Wnt/β-catenin signaling extends throughout the pronephric primordium and is essential for the development of proximal and distal tubules of the pronephros as well as for the development of the duct and glomus. Although less pronounced than effects upon later pronephric tubule differentiation, inhibition of the Wnt/β-catenin pathway decreased expression of early pronephric mesenchymal markers indicating it is also needed in early pronephric patterning. We find that upstream inhibition of Wnt/β-catenin signals in zebrafish likewise reduces pronephric epithelial tubulogenesis. We also find that exogenous activation of Wnt/β-catenin signaling within the Xenopus pronephric field results in significant tubulogenic losses. Together, we propose Wnt/β-catenin signaling is required for pronephric tubule, duct and glomus formation in Xenopus laevis, and this requirement is conserved in zebrafish pronephric tubule formation.

Phosphoproteomic Profiling Reveals Vasopressin-Regulated Phosphorylation Sites in Collecting Duct

“…30 It is involved in the highly conserved canonical Wnt signaling pathway. Although involvement of ␤-catenin in the embryonic development of the collecting duct has been well studied, [31][32][33] there is only indirect evidence regarding its relationship to vasopressin signaling in the mature collecting duct. 23 The amino acid sequence surrounding Ser-552 of ␤-catenin (…QRRTS 552 MGGT…) is consistent with a PKA motif.…”

Lung epithelial branching program antagonizes alveolar differentiation

“…Xenopus laevis embryos were obtained and grown using standard methods (51). At Nieuwkoop and Faber stages 36, 38, 40, and 42, embryos were fixed as previously described (52) and kept in methanol at −20°C.…”

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…Again, form the panel of potential inhibitors only EnR-Lef-1-GR (Lyons et al, 2009) and Tcf3∆C-GR (Pukrop et al, 2001) were able to ventralize Xenopus embryos (Fig.4.6). …”