The Wave complex controls epidermal morphogenesis and proliferation by suppressing Wnt-Sox9 signaling.
J Cell Biol
; 218(4): 1390-1406, 2019 04 01.
Article
em En
| MEDLINE
| ID: mdl-30867227
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/ß-catenin signaling. Our results identify a novel role for Wave complex- and actin-regulated signaling via Wnt and SOX9 in skin development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Queratinócitos
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Proteínas do Citoesqueleto
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Proteínas Adaptadoras de Transdução de Sinal
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Proliferação de Células
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Epiderme
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Família de Proteínas da Síndrome de Wiskott-Aldrich
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Fatores de Transcrição SOX9
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Via de Sinalização Wnt
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Israel