Document Detail

Developmental roles for Srf, cortical cytoskeleton and cell shape in epidermal spindle orientation.
MedLine Citation:
PMID:  21336301     Owner:  NLM     Status:  MEDLINE    
During development, a polarized epidermal sheet undergoes stratification and differentiation to produce the skin barrier. Through mechanisms that are poorly understood, the process involves actin dynamics, spindle reorientation and Notch signalling. To elucidate how epidermal embryogenesis is governed, we conditionally targeted serum response factor (Srf), a transcription factor that is essential for epidermal differentiation. Unexpectedly, previously ascribed causative defects are not responsible for profoundly perturbed embryonic epidermis. Seeking the mechanism for this, we identified actins and their regulators that were downregulated after ablation. Without Srf, cells exhibit a diminished cortical network and in mitosis, they fail to round up, features we recapitulate with low-dose actin inhibitors in vivo and shRNA-knockdown in vitro. Altered concomitantly are phosphorylated ERM and cortical myosin-IIA, shown in vitro to establish a rigid cortical actomyosin network and elicit critical shape changes. We provide a link between these features and Srf loss, and we show that the process is physiologically relevant in skin, as reflected by defects in spindle orientation, asymmetric cell divisions, stratification and differentiation.
Chen Luxenburg; H Amalia Pasolli; Scott E Williams; Elaine Fuchs
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-20
Journal Detail:
Title:  Nature cell biology     Volume:  13     ISSN:  1476-4679     ISO Abbreviation:  Nat. Cell Biol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-02     Completed Date:  2011-04-27     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  203-14     Citation Subset:  IM    
Copyright Information:
© 2011 Macmillan Publishers Limited. All rights reserved.
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MeSH Terms
Actins / chemistry
Actomyosin / chemistry
Cell Differentiation
Cytoskeleton / metabolism*
Epidermis / metabolism*
Mice, Transgenic
Serum Response Factor / metabolism*
Skin / pathology
Spindle Apparatus*
Grant Support
R01 AR027883/AR/NIAMS NIH HHS; R01 AR027883-29/AR/NIAMS NIH HHS; R01AR27883/AR/NIAMS NIH HHS; R37 AR027883/AR/NIAMS NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Actins; 0/Serum Response Factor; 9013-26-7/Actomyosin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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