Non‐canonical wnt signals antagonize and canonical wnt signals promote cell proliferation in early kidney development

Abstract

Canonical and non-canonical wnt signals often have opposed roles. In this report, we use developing Xenopus embryos to demonstrate a novel anti-proliferative role for non-canonical wnt signals in the very earliest stages of kidney development. Non-canonical wnt signals were down-regulated using PDZ domain mutants of dishevelled 2 and up-regulated using wild-type vang-like 2, while canonical signals were manipulated using dominant-negative forms of lef1 or treatment with lithium. When non-canonical signals are down-regulated in the developing Xenopus pronephros, cell proliferation rates increased and when canonical signals were shutdown the opposite occurred. Treatment with lithium chloride has a powerful pro-proliferative effect on the forming nephric primordium. Together these data show that in addition to previously documented antagonisms between these distinct wnt signaling pathways, they also have opposing effects on cell division.