Rho kinases play an obligatory role in vertebrate embryonic organogenesis

Rho-associated kinases (Rho kinases), which are downstream effectors of Rho A GTPase, regulate diverse cellular functions including actin cytoskeletal organization. We have demonstrated that Rho kinases also direct the early s tages of chick and mouse embryonic morphogenesis. We observed that Rho kina se transcripts were enriched in cardiac mesoderm, lateral plate mesoderm an d the neural plate. Treatment of neurulating embryos with Y27632, a specifi c inhibitor of Rho kinases, blocked migration and fusion of the bilateral h eart primordia, formation of the brain and neural tube, caudalward movement of Hensen's node, and establishment of normal left-right asymmetry. Moreov er, Y27632 induced precocious expression of cardiac alpha -actin, an early marker of cardiomyocyte differentiation, coincident with the upregulated ex pression of serum response factor and GATA4. In addition, specific antisens e oligonucleotides significantly diminished Rho kinase mRNA levels and repl icated 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.