The Wave Complex Controls Epidermal Morphogenesis and Proliferation by Suppressing Wnt-Sox9 Signaling

The study identified a crucial role for the Wave complex proteins ABI1 and Wave2 in regulating epidermal morphogenesis and proliferation by suppressing Wnt–Sox9 signaling. In utero RNAi-mediated silencing of Abi1 or Wasf2 led to cellular hyperproliferation, architectural defects in the interfollicular epidermis (IFE), and delayed hair follicle growth. Aberrant expression of SOX9, a hair follicle growth regulator, was observed throughout the IFE of mutant embryos, and its overexpression mimicked the loss-of-function phenotype of the Wave complex. Additionally, Wnt signaling, which influences SOX9+ cell specification, was up-regulated in the absence of Wave complex function. The study demonstrated that the Wave complex regulates filamentous actin content, and a decrease in actin levels was sufficient to increase Wnt/β-catenin signaling, highlighting a novel role for Wave complex– and actin-regulated signaling in skin development.