JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

Abstract

The Wnt/planar cell polarity (PCP) pathway plays a critical role in wing, eye, and sensory bristle development of Drosophila and in convergent extension (CE) movements during vertebrate gastrulation. In Drosophila, Jun N-terminal kinase (JNK) and Rho-associated kinase (ROK) participate in RhoA-mediated PCP pathway during eye and wing development. In mammalian cells, Rac1 and Cdc42 but not RhoA are required for JNK activation by Wnt/PCP signals. However, there has been no evidence that Rho GTPases regulate JNK activation in Wnt/PCP pathway during Xenopus CE movements. Here, we report that Xenopus RhoA (XRhoA), but not Xenopus Cdc42 (XCdc42), is essential for JNK activation downstream of the Wnt/PCP pathway during Xenopus CE movements, and the phenotypic effect of loss of XRhoA function was rescued by Xenopus JNK1 (XeJNK1). In addition, XRhoA rescues the inhibition of CE movements by the DEP domain deletion mutant of Xenopus Dsh (Xdsh-⌬DEP), which has dominant negative (DN) effects on JNK activation, and the PDZ domain deletion mutant of Xdsh (Xdsh-⌬PDZ). Moreover, we demonstrate that Xenopus Rho-associated kinase ␣ (xROK␣), which is expressed mainly in mesoderm and ectoderm that undergo extensive cell rearrangements, regulates CE movements without affecting gene expression, and injection of xROK␣ rescued the inhibition of CE movements caused by DN XRhoA. Finally, we show that ROK␣ and JNK synergistically rescued embryos overexpressing DN XRhoA, which exhibit gastrulation defects, although ROK␣ is not required for JNK activation. Together, these data suggest that JNK and ROK␣ function in the noncanonical Wnt/RhoA pathway to regulate Xenopus CE movements. Developmental Dynamics 232: 958 -968, 2005.

Morphogenesis of the primitive gut tube is generated by Rho/ROCK/myosin II–mediated endoderm rearrangements

“…To test the hypothesis that Rho signaling also plays a role in tissue elongation and/or endoderm rearrangements during gut tube morphogenesis, we confirmed that the genes encoding Xenopus RhoA, XRhoA (Wunnenberg-Stapleton et al, 1999), and a downstream effector of RhoA, a Rho-associated kinase, XRoka (Kim and Han, 2005), are expressed in the developing Xenopus gut tube, including the endoderm layer (Supp. Fig.…”

“…Rho GTPase signaling controls changes in cell shape, adhesion, and rearrangement during tissue elongation (Evers et al, 2000;Settleman, 2001;Etienne-Manneville and Hall, 2002;Marlow et al, 2002;Habas et al, 2003;Bertet et al, 2004;Kim and Han, 2005;Zhu et al, 2005). Therefore, we hypothesized that the above gut elongation defects may be the result of aberrant endoderm cell shape change, adhesion, and/or rearrangement.…”

“…In multiple embryonic contexts, the Rho GTPase signaling pathway plays key roles in controlling tissue elongation by intercellular rearrangement (Marlow et al, 2002;Bertet et al, 2004;Kim and Han, 2005;Zhu et al, 2005;Lai et al, 2005;Diogon et al, 2007;Weiser et al, 2007;Skoglund et al, 2008). To test the hypothesis that Rho signaling also plays a role in tissue elongation and/or endoderm rearrangements during gut tube morphogenesis, we confirmed that the genes encoding Xenopus RhoA, XRhoA (Wunnenberg-Stapleton et al, 1999), and a downstream effector of RhoA, a Rho-associated kinase, XRoka (Kim and Han, 2005), are expressed in the developing Xenopus gut tube, including the endoderm layer (Supp.…”

Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii

“…In many vertebrate morphogenetic processes, Rok has been shown to act as an effector of the PCP pathway [40][41][42][43][44] . We therefore isolated and characterized the expression patterns of several genes encoding members of the PCP pathway in Platynereis.…”

Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling

“…Our results suggest that Dsh (PDZ domain) and JNK activity are required for gut elongation, whereas ROCK and PKC activity are required for midline convergence of the foregut organs, with Dsh (DEP domain) and Rac activity being essential for both convergence and extension. This is reminiscent of CE in the gastrula mesoderm where Wnt11 signals via Dsh (both the PDZ and DEP domains), Rac, JNK, Rho, ROCK, and PKC to coordinate dynamic cell behaviors, with each of the components having both distinct and overlapping functions (Yamanaka et al 2002;Habas et al 2003;Kinoshita et al 2003;Tahinci and Symes 2003;Kim and Han 2005).…”