Invited: Novel Functions for the Actin Cytoskeleton in Skin Development

The skin epidermis is a stratified epithelium that functions as a barrier. Epidermal development requires tight control over the activity of several signaling pathways; however, the mechanisms that coordinate these events remain poorly understood. We identify a novel role for the Wave complex proteins ABI1 and Wave2 in regulating signals that control epidermal shape and growth. In utero RNAi-mediated loss-of-function of Wave complex activity induced cellular hyperproliferation and defects in the organization of the interfollicular epidermis and delayed hair follicle growth. Unexpectedly, SOX9, a hair follicle growth regulator, was ectopically 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+ expression in the epidermis, was upregulated in Wave complex loss-of-function interfollicular epidermis. We also found that the Wave complex regulates filamentous (F-)actin content and that a decrease in actin levels is sufficient to increase nuclear β-catenin levels in vitro, and to elevate Wnt signaling in vivo. Our results identify a novel role for Wave complex- and actin-regulated signaling via Wnt and SOX9 in epidermal development.