The prickle-Related Gene in Vertebrates Is Essential for Gastrulation Cell Movements

Abstract

Involving dynamic and coordinated cell movements that cause drastic changes in embryo shape, gastrulation is one of the most important processes of early development. Gastrulation proceeds by various types of cell movements, including convergence and extension, during which polarized axial mesodermal cells intercalate in radial and mediolateral directions and thus elongate the dorsal marginal zone along the anterior-posterior axis [1,2]. Recently, it was reported that a noncanonical Wnt signaling pathway, which is known to regulate planar cell polarity (PCP) in Drosophila [3,4], participates in the regulation of convergent extension movements in Xenopus as well as in the zebrafish embryo [5-8]. The Wnt5a/Wnt11 signal is mediated by members of the seven-pass transmembrane receptor Frizzled (Fz) and the signal transducer Dishevelled (Dsh) through the Dsh domains that are required for the PCP signal [6-8]. It has also been shown that the relocalization of Dsh to the cell membrane is required for convergent extension movements in Xenopus gastrulae. Although it appears that signaling via these components leads to the activation of JNK [9,10] and rearrangement of microtubules, the precise interplay among these intercellular components is largely unknown. In this study, we show that Xenopus prickle (Xpk), a Xenopus homolog of a Drosophila PCP gene [11-13], is an essential component for gastrulation cell movement. Both gain-of-function and loss-of-function of Xpk severely perturbed gastrulation and caused spina bifida embryos without affecting mesodermal differentiation. We also demonstrate that XPK binds to Xenopus Dsh as well as to JNK. This suggests that XPK plays a pivotal role in connecting Dsh function to JNK activation.

Vang-like protein 2 and Rac1 interact to regulate adherens junctions

“…We conclude that both Vangl2 gain-of-function and loss-offunction disturb the localization of actin and actin-associated components of adherens junctions, such as -catenin and Ncadherin, in agreement with previous reports on PCP protein function (Carreira-Barbosa et al, 2003;Darken et al, 2002;Goto and Keller, 2002;Takeuchi et al, 2003;Veeman et al, 2003). Furthermore, the PDZ-binding domain seems to be essential in mediating this effect.…”

“…They were first characterized as regulators of convergent extension, a process during gastrulation and neurulation where lateral cells migrate and intercalate at the midline, thus narrowing and elongating the embryo. Both reduced and increased levels of PCP proteins disturb convergent extension, indicating a dose-dependent effect (CarreiraBarbosa et al, 2003;Darken et al, 2002;Goto and Keller, 2002;Takeuchi et al, 2003;Veeman et al, 2003). In addition to their role in convergent extension, Vangl2, Celsr1 and Scrb1 also regulate PCP in the mammalian inner ear (Montcouquiol et al, 2006).…”

Molecular regulation of kidney development: is the answer blowing in the Wnt?

“…Removal of Dvl, Vangl and prickle orthologs results in convergent extension defects during neurulation, cochlear formation and gastrulation, indicating that PCP signaling is required for these morphogenetic movements in vertebrates [93][94][95][96][97][98][99]. Cell intercalation has not been demonstrated during the development of the mouse kidney tubules although it does occur during the development of the fly Malpighian tubules [100].…”

Essential role of non-canonical Wnt signalling in neural crest migration

“…Perturbation of non-canonical Wnt signalling disrupts the mediolateral elongation and alignment of dorsal mesodermal cells, and the mediolateral stabilization of cell protrusions (Wallingford et al, 2000). In addition, interference with the non-canonical Wnt signalling pathway of zebrafish, Xenopus or mouse embryos, either genetically or by the use of morpholinos, produces defects in convergent extension of the mesoderm and failures in neural tube closure (Carreira-Barbosa et al, 2003;Curtin et al, 2003;Darken et al, 2002;Goto and Keller, 2002;Heisenberg et al, 2000;Jessen et al, 2002;Kibar et al, 2001;Kilian et al, 2003;Park and Moon, 2002;Rauch et al, 1997;Takeuchi et al, 2003;Veeman et al, 2003b).…”