Rho kinases play an obligatory role in vertebrate embryonic organogenesis.
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 alpha-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.
Wei
L
L
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Roberts
W
W
Wang
L
L
Yamada
M
M
Zhang
S
S
Zhao
Z
Z
Rivkees
S A
SA
Schwartz
R J
RJ
Imanaka-Yoshida
K
K
D000577:Amides / Q000494:pharmacology; D000818:Animals; D016764:Cell Polarity; D002642:Chick Embryo; D046508:Culture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004622:Embryo, Mammalian / Q000002:abnormalities; D005314:Embryonic and Fetal Development / Q000502:physiology*; D004707:Endoderm / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050992:GATA5 Transcription Factor; D006321:Heart / Q000196:embryology; D047908:Intracellular Signaling Peptides and Proteins; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis; D054460:rho-Associated Kinases
D000577:Amides; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050992:GATA5 Transcription Factor; C494756:Gata5 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D011725:Pyridines; D014157:Transcription Factors; C108830:Y 27632; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases