The Wave complex controls epidermal morphogenesis and proliferation by suppressing Wnt–Sox9 signaling
| Autor: | Krishnanand Padmanabhan, Shaul Raviv, Jonathan Cohen, Arad Soffer, Chen Luxenburg, Orit Adir |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Keratinocytes
macromolecular substances Biology Filamentous actin Article Mice 03 medical and health sciences 0302 clinical medicine Morphogenesis medicine Animals Gene silencing Gene Silencing Phosphorylation Wnt Signaling Pathway Cells Cultured beta Catenin Research Articles Actin Adaptor Proteins Signal Transducing Cell Proliferation 030304 developmental biology 0303 health sciences integumentary system Epidermis (botany) Wnt signaling pathway Gene Expression Regulation Developmental SOX9 Transcription Factor Cell Biology Hair follicle ABI1 Wiskott-Aldrich Syndrome Protein Family Cell biology Cytoskeletal Proteins medicine.anatomical_structure Epidermis Signal transduction Hair Follicle 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | The Wave complex promotes Arp2/3-mediated actin polymerization. Cohen et al. show that Wave complex activity regulates epidermal shape and growth. Without Wave complex activity, F-actin content is down-regulated and ectopic activity of the Wnt/β-catenin–SOX9 pathway is triggered. This activity induces epidermal hyperproliferation and disrupts tissue architecture. 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. |
| Databáze: | OpenAIRE |
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