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N-wasp is a novel regulator of hair-follicle cycling that controls antiproliferative tgf  pathways

Lefever, T.
; 
Pedersen, E.
; 
Basse, A.
; 
Paus, R.
; 
Quondamatteo, F.
; 
Stanley, A. C.
; 
Langbein, L.
; 
Wu, X.
; 
Wehland, J.
; 
Lommel, S.
... show 1 more
Identifiers
http://hdl.handle.net/10379/12413
https://doi.org/10.13025/27315
Repository DOI
10.1242/jcs.053835
Publication Date
2009-12-16
Keywords
n-wasp, hair cycling, keratinocytes, comprehensive guide, keratinocyte growth, skin development, transgenic mice, in-vivo, differentiation, epidermis, motility, overexpression, classification
Type
Article
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Citation
Lefever, T. Pedersen, E.; Basse, A.; Paus, R.; Quondamatteo, F.; Stanley, A. C.; Langbein, L.; Wu, X.; Wehland, J.; Lommel, S.; Brakebusch, C. (2009). N-wasp is a novel regulator of hair-follicle cycling that controls antiproliferative tgf  pathways. Journal of Cell Science 123 (1), 128-140
Abstract
N-WASP is a cytoplasmic molecule mediating Arp2/3 nucleated actin polymerization. Mice with a keratinocyte-specific deletion of the gene encoding N-WASP showed normal interfollicular epidermis, but delayed hair-follicle morphogenesis and abnormal hair-follicle cycling, associated with cyclic alopecia and prolonged catagen and telogen phases. The delayed anagen onset correlated with an increased expression of the cell-cycle inhibitor p21CIP, and increased activity of the TGF beta pathway, a known inducer of p21CIP expression. Primary N-WASP-null keratinocytes showed reduced growth compared with control cells and enhanced expression of the gene encoding the cell-cycle inhibitor p15INK4B, a TGF beta target gene. Inhibition of TGF beta signaling blocked overexpression of p15INK4B and restored proliferation of N-WASP-deficient keratinocytes in vitro. However, induction of N-WASP gene deletion in vitro did not result in obvious changes in TGF beta signaling or growth of keratinocytes, indicating that the in vivo environment is required for the phenotype development. These data identify the actin nucleation regulator N-WASP as a novel element of hair-cycle control that modulates the antiproliferative and pro-apoptotic TGF. pathway in keratinocytes in vivo and in vitro.
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Publisher
The Company of Biologists
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Attribution-NonCommercial-NoDerivs 3.0 Ireland
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Externally hosted open access publications with University of Galway authors (2)