Rho kinases play an obligatory role in vertebrate embryonic organogenesis

L. Wei, W. Roberts, L. Wang, M. Yamada, S. Zhang, Z. Zhao, S. A. Rivkees, R. J. Schwartz, K. Imanaka-Yoshida

Research output: Contribution to journalArticle

186 Scopus citations

Abstract

Rho-associated kinases (Rho kinases), which are downstream effectors of RhoA GTPase, regulate diverse cellular functions including actin cytoskeletal organization. We have demonstrated that Rho kinases also direct the early stages of chick and mouse embryonic morphogenesis. We observed that Rho kinase transcripts were enriched in cardiac mesoderm, lateral plate mesoderm and the neural plate. Treatment of neurulating embryos with Y27632, a specific inhibitor of Rho kinases, blocked migration and fusion of the bilateral heart primordia, formation of the brain and neural tube, caudalward movement of Hensen's node, and establishment of normal left-right asymmetry. Moreover, Y27632 induced precocious expression of cardiac α-actin, an early marker of cardiomyocyte differentiation, coincident with the upregulated expression of serum response factor and GATA4. In addition, specific antisense oligonucleotides significantly diminished Rho kinase mRNA levels and replicated many of the teratologies induced by Y27632. Thus, our study reveals new biological functions for Rho kinases in regulating major morphogenetic events during early chick and mouse development.

Original languageEnglish (US)
Pages (from-to)2953-2962
Number of pages10
JournalDevelopment
Volume128
Issue number15
StatePublished - Sep 1 2001
Externally publishedYes

Keywords

  • Cardia bifida
  • Cardiomyocyte differentiation
  • Chick
  • Rho kinase
  • Y27632

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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  • Cite this

    Wei, L., Roberts, W., Wang, L., Yamada, M., Zhang, S., Zhao, Z., Rivkees, S. A., Schwartz, R. J., & Imanaka-Yoshida, K. (2001). Rho kinases play an obligatory role in vertebrate embryonic organogenesis. Development, 128(15), 2953-2962.