The Wave complex controls epidermal morphogenesis and proliferation by suppressing Wnt-Sox9 signaling

Jonathan Cohen, Shaul Raviv, Orit Adir, Krishnanand Padmanabhan, Arad Soffer, Chen Luxenburg

Research output: Contribution to journalArticlepeer-review

Abstract

Development of the skin epidermis requires tight spatiotemporal control over the activity of several signaling pathways; however, the mechanisms that orchestrate these events remain poorly understood. Here, we identify a key role for the Wave complex proteins ABI1 and Wave2 in regulating signals that control epidermal shape and growth. In utero RNAi-mediated silencing of Abi1 or Wasf2 induced cellular hyperproliferation and defects in architecture of the interfollicular epidermis (IFE) and delayed hair follicle growth. Unexpectedly, SOX9, a hair follicle growth regulator, was aberrantly expressed throughout the IFE of the mutant embryos, and its forced overexpression mimicked the Wave complex loss-of-function phenotype. Moreover, Wnt signaling, which regulates SOX9+ cell specification, was up-regulated in Wave complex loss-of-function IFE. Importantly, we show that the Wave complex regulates filamentous actin content and that a decrease in actin levels is sufficient to elevate Wnt/β-catenin signaling. Our results identify a novel role for Wave complex- and actin-regulated signaling via Wnt and SOX9 in skin development.

Original languageEnglish
Pages (from-to)1390-1406
Number of pages17
JournalJournal of Cell Biology
Volume218
Issue number4
DOIs
StatePublished - 2019

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