ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.
Rho-associated kinase (ROCK) I mediates signaling from Rho to the actin cytoskeleton. To investigate the in vivo functions of ROCK-I, we generated ROCK-I-deficient mice. Loss of ROCK-I resulted in failure of eyelid closure and closure of the ventral body wall, which gave rise to the eyes open at birth and omphalocele phenotypes in neonates. Most ROCK-I(-/-) mice died soon after birth as a result of cannibalization of the omphalocele by the mother. Actin cables that encircle the eye in the epithelial cells of the eyelid were disorganized and accumulation of filamentous actin at the umbilical ring was impaired, with loss of phosphorylation of the myosin regulatory light chain (MLC) at both sites, in ROCK-I(-/-) embryos. Stress fiber formation and MLC phosphorylation induced by EGF were also attenuated in primary keratinocytes from ROCK-I(-/-) mice. These results suggest that ROCK-I regulates closure of the eyelids and ventral body wall through organization of actomyosin bundles.
Shimizu
Yoshihiko
Y
Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
Thumkeo
Dean
D
Keel
Jeongsin
J
Ishizaki
Toshimasa
T
Oshima
Hiroko
H
Oshima
Masanobu
M
Noda
Yoichi
Y
Matsumura
Fumio
F
Taketo
Makoto M
MM
Narumiya
Shuh
S
D034861:Abdominal Wall / Q000196:embryology*; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005143:Eyelids / Q000002:abnormalities / Q000196:embryology* / Q000648:ultrastructure; D005982:Glutathione Transferase / Q000378:metabolism; D006554:Hernia, Umbilical / Q000209:etiology; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000187:drug effects; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects; D014945:Wound Healing / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism; D054460:rho-Associated Kinases
D047908:Intracellular Signaling Peptides and Proteins; D018994:Myosin Light Chains; D011993:Recombinant Fusion Proteins; D004815:Epidermal Growth Factor; D000205:Actomyosin; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D001616:beta-Galactosidase