Document Detail

Macroscopic stiffening of embryonic tissues via microtubules, RhoGEF and the assembly of contractile bundles of actomyosin.
MedLine Citation:
PMID:  20630946     Owner:  NLM     Status:  MEDLINE    
During morphogenesis, forces generated by cells are coordinated and channeled by the viscoelastic properties of the embryo. Microtubules and F-actin are considered to be two of the most important structural elements within living cells accounting for both force production and mechanical stiffness. In this paper, we investigate the contribution of microtubules to the stiffness of converging and extending dorsal tissues in Xenopus laevis embryos using cell biological, biophysical and embryological techniques. Surprisingly, we discovered that depolymerizing microtubules stiffens embryonic tissues by three- to fourfold. We attribute tissue stiffening to Xlfc, a previously identified RhoGEF, which binds microtubules and regulates the actomyosin cytoskeleton. Combining drug treatments and Xlfc activation and knockdown lead us to the conclusion that mechanical properties of tissues such as viscoelasticity can be regulated through RhoGTPase pathways and rule out a direct contribution of microtubules to tissue stiffness in the frog embryo. We can rescue nocodazole-induced stiffening with drugs that reduce actomyosin contractility and can partially rescue morphogenetic defects that affect stiffened embryos. We support these conclusions with a multi-scale analysis of cytoskeletal dynamics, tissue-scale traction and measurements of tissue stiffness to separate the role of microtubules from RhoGEF activation. These findings suggest a re-evaluation of the effects of nocodazole and increased focus on the role of Rho family GTPases as regulators of the mechanical properties of cells and their mechanical interactions with surrounding tissues.
Jian Zhou; Hye Young Kim; James H-C Wang; Lance A Davidson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-07-14
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  137     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-28     Completed Date:  2010-08-20     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  2785-94     Citation Subset:  IM    
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA.
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MeSH Terms
Actomyosin / metabolism*
Embryo, Nonmammalian / cytology*,  metabolism
Guanine Nucleotide Exchange Factors / metabolism*
Microtubules / metabolism*
Xenopus laevis / embryology*,  metabolism
Grant Support
Reg. No./Substance:
0/Guanine Nucleotide Exchange Factors; 0/rho guanine nucleotide exchange factors; 9013-26-7/Actomyosin

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