TY - JOUR
T1 - The Wave complex controls epidermal morphogenesis and proliferation by suppressing Wnt-Sox9 signaling
AU - Cohen, Jonathan
AU - Raviv, Shaul
AU - Adir, Orit
AU - Padmanabhan, Krishnanand
AU - Soffer, Arad
AU - Luxenburg, Chen
N1 - Publisher Copyright: © 2019 Cohen et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064200417&partnerID=8YFLogxK
U2 - https://doi.org/10.1083/jcb.201807216
DO - https://doi.org/10.1083/jcb.201807216
M3 - مقالة
SN - 0021-9525
VL - 218
SP - 1390
EP - 1406
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -