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Published online 7 March 2005. doi:10.1083/jcb.200411179
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 168, Number 6, 941-953
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Article

 ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles

Yoshihiko Shimizu1,2, Dean Thumkeo1, Jeongsin Keel1, Toshimasa Ishizaki1, Hiroko Oshima1, Masanobu Oshima1, Yoichi Noda2, Fumio Matsumura3, Makoto M. Taketo1, and Shuh Narumiya1

1 Department of Pharmacology, Kyoto University Faculty of Medicine, Sakyo-ku, Kyoto 606-8501, Japan
2 Department of Obstetrics and Gynecology, Shiga University of Medical Science, Ohtsu, Shiga 520-2191, Japan
3 Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08855

Correspondence to Shuh Narumiya: snaru{at}mfour.med.kyoto-u.ac.jp

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.

Y. Shimizu and D. Thumkeo contributed equally to this work.

J. Keel was deceased on 6 September 2000.

Abbreviations used in this paper: {alpha}-SMA, {alpha}-smooth muscle actin; dpc, d postcoitum; EGFR, EGF receptor; EOB, eyes open at birth; JNK, c-Jun NH2-terminal kinase; MLC, myosin regulatory light chain; ROCK, Rho-associated kinase.


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