title: ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.
abstract: 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.
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Dean
authors.initials: D
authors.lastname: Thumkeo
authors.forename: Jeongsin
authors.initials: J
authors.lastname: Keel
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Oshima
authors.forename: Masanobu
authors.initials: M
authors.lastname: Oshima
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Noda
authors.forename: Fumio
authors.initials: F
authors.lastname: Matsumura
authors.forename: Makoto M
authors.initials: MM
authors.lastname: Taketo
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: 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
chemical_list: 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