ROCK‐I and ROCK‐II cooperatively regulate closure of eyelid and ventral body wall in mouse embryo

Abstract

Rho-associated kinase (ROCK) is

c-Jun, at the crossroad of the signaling network

“…Besides MAP3K1, embryonic eyelid closure depends on signals derived from WNT, Sonic hedgehog, BMP/Activin, FGF and EGF (Luetteke et al, 1993;Mine et al, 2005;Gage et al, 2008;Huang et al, 2009). In addition, eyelid closure requires the participation of a number of intracellular signaling kinases, such as JNK, ROCK and CDH1, and nuclear transcription factors, such as c-Jun, Fra-2, FOXL2, SMAD and GRHL3 (McHenry et al, 1998;Li et al, 2003;Zenz et al, 2003;Zhang et al, 2003;Uda et al, 2004;Thumkeo et al, 2005;Takatori et al, 2008;Yu et al, 2008;Naoe et al, 2010). While how these factors are organized into a morphogenetic network for eyelid closure has not been well understood, molecular analyses of these mice have begun to unveil that some of the factors are organized into concerted signal transduction cascades.…”

Rho kinase in the regulation of cell death and survival

“…ROCK2 -/-mice in a mixed genetic background between 129/SvJ and C57BL/6N are embryonic lethal because of placental dysfunction, and have intrauterine growth retardation caused by thrombus formation in the labyrinth layer of the placenta, indicating that there is no compensation for the loss of ROCK2 by ROCK1 [135]. Interestingly, ROCK2 -/-mice under C57BL/6N genetic background exhibit not only the placental phenotype but also EOB and omphalocele phenotype [136], indicating that genetic background affects the EOB and omphalocele phenotype in ROCK2 -/-mice. In addition the shared EOB and omphalocele phenotype in ROCK1 -/-and ROCK2 -/-mice under C57BL/6N genetic background indicates that they act together to regulate the assembly of actin bundles essential for closure of eyelid and ventricular body wall in mouse embryos.…”

A new serine/threonine protein kinase,Omphk1, essential to ventral body wall formation

“…Particularly RockI and RockII of this group are Rho effectors and play important roles in cell morphology and behavior (Riento and Ridley, 2003); the small GTPase Rho regulates several steps of actin dynamics (EtienneManneville and Hall, 2002). Moreover, they are demonstrated to regulate actomyosin contraction or actin bundle assembly in the epithelium for the closure of the ventral body wall Thumkeo et al, 2005). The reason why there is no apparent gross morphological defect in epidermis against the ubiquitous Omphk1 expression in this tissue (Fig.…”

“…AP-2␣ (Brewer and Williams, 2004a), Hoxb2/b4 double (Manley et al, 2001), Tgf␤2/␤3 double (Dunker and Krieglstein, 2002), and Mab21l2 (Yamada et al, 2004) mutants have defects in the primary body wall formation. The AP-2␣ mutant also lacks sternal and abdominal bands (Brewer and Williams, 2004a), and several mutants are known that have defects in the migration of the bands and/or in the subsequent clo-sure of the ventral body wall (Suzuki et al, 1996;Eggenschwiler et al, 1997;Zhang et al, 1997;Kitamura et al, 1999;Carter et al, 2000;Rauch et al, 2000;Doyonnas et al, 2001;Ogi et al, 2005;Thumkeo et al, 2005). However, the number of genes that participate in the ventral body wall formation is still too limited to discuss the molecular events of formation of this wall or pathologies of human defects.…”