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A focal adhesion protein‐based mechanochemical checkpoint regulates cleft progression during branching morphogenesis
Author(s) -
Daley William P.,
Kohn Joshua M.,
Larsen Melinda
Publication year - 2011
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.22714
Subject(s) - focal adhesion , integrin , microbiology and biotechnology , ptk2 , morphogenesis , vinculin , fibronectin , biology , myosin , adhesion , signal transduction , kinase , chemistry , protein kinase a , biochemistry , extracellular matrix , receptor , mitogen activated protein kinase kinase , organic chemistry , gene
Cleft formation is the initial step of branching morphogenesis in many organs. We previously demonstrated that ROCK 1 regulates a nonmuscle myosin II‐dependent mechanochemical checkpoint to transition initiated clefts to progressing clefts in developing submandibular salivary glands. Here, we report that ROCK‐mediated integrin activation and subsequent formation of focal adhesion complexes comprise this mechanochemical checkpoint. Inhibition of ROCK1 and nonmuscle myosin II activity decreased integrin β1 activation in the cleft region and interfered with localization and activation of focal adhesion complex proteins, such as focal adhesion kinase (FAK). Inhibition of FAK activity also prevented cleft progression, by disrupting recruitment of the focal adhesion proteins talin and vinculin and subsequent fibronectin assembly in the cleft region while decreasing ERK1/2 activation. These results demonstrate that inside‐out integrin signaling leading to a localized recruitment of active FAK‐containing focal adhesion protein complexes generates a mechanochemical checkpoint that facilitates progression of branching morphogenesis. Developmental Dynamics 240:2069–2083, 2011. © 2011 Wiley‐Liss, Inc.