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Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation
Author(s) -
Sakabe Masahide,
Ikeda Kazuo,
Nakatani Kazuki,
Kawada Norifumi,
ImanakaYoshida Kyoko,
Yoshida Toshimichi,
Yamagishi Toshiyuki,
Nakajima Yuji
Publication year - 2006
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.20648
Subject(s) - rock1 , mesenchymal stem cell , microbiology and biotechnology , rho associated protein kinase , biology , rho kinase inhibitor , rac1 , actin , kinase , motility , cell migration , myosin , cell , protein kinase a , signal transduction , biochemistry
Rho‐associated kinase (ROCK) is a downstream effector of small Rho‐GTPases, and phosphorylates several substrates to regulate cell functions, including actin cytoskeletal reorganization and cellular motility. Endothelial–mesenchymal transformation (EMT) is a critical event in the formation of valves and septa during cardiogenesis. It has been reported that ROCK plays an important role in the regulation of endocardial cell differentiation and migration during mouse cardiogenesis (Zhao and Rivkees [2004] Dev. Biol. 275:183–191). Immunohistochemistry showed that, during chick cardiogenesis, ROCK1 and ‐2 were expressed in the transforming and migrating endothelial/mesenchymal cells in the outflow tract (OT) and atrioventricular (AV) canal regions from which valvuloseptal endocardial cushion tissue would later develop. Treatment with Y27632, a specific ROCK inhibitor, of cultured AV explants or AV endothelial monolayers of stage 14‐minus heart (preactivated stage for EMT) on three‐dimensional collagen gel perturbed the seeding of mesenchymal cells into the gel lattice. In these experiments, Y27632 did not suppress the expression of an early transformation marker, smooth muscle α‐actin. Moreover, Y27632 inhibited the mesenchymal invasion in stage 14–18 AV explants, in which endothelial cells had committed to undergo EMT. ML‐9, a myosin light chain kinase inhibitor, also inhibited the mesenchymal invasion in cultured AV explants. These results suggest that ROCKs have a critical role in the mesenchymal cell invasion/migration that occurs at the late onset of EMT. Developmental Dynamics 235:94–104, 2006. © 2005 Wiley‐Liss, Inc.