Prickle 1 regulates cell movements during gastrulation and neuronal migration in zebrafish

Abstract

During vertebrate gastrulation, mesodermal and ectodermal cells undergo convergent extension, a process characterised by prominent cellular rearrangements in which polarised cells intercalate along the medio-lateral axis leading to elongation of the antero-posterior axis. Recently, it has become evident that a noncanonical Wnt/Frizzled (Fz)/Dishevelled (Dsh)signalling pathway, which is related to the planar-cell-polarity (PCP) pathway in flies, regulates convergent extension during vertebrate gastrulation. Here we isolate and functionally characterise a zebrafish homologue of Drosophila prickle (pk), a gene that is implicated in the regulation of PCP. Zebrafish pk1 is expressed maternally and in moving mesodermal precursors. Abrogation of Pk1 function by morpholino oligonucleotides leads to defective convergent extension movements, enhances the silberblick (slb)/wnt11 and pipetail (Ppt)/wnt5phenotypes and suppresses the ability of Wnt11 to rescue the slbphenotype. Gain-of-function of Pk1 also inhibits convergent extension movements and enhances the slb phenotype, most likely caused by the ability of Pk1 to block the Fz7-dependent membrane localisation of Dsh by downregulating levels of Dsh protein. Furthermore, we show that pk1interacts genetically with trilobite(tri)/strabismus to mediate the caudally directed migration of cranial motor neurons and convergent extension. These results indicate that, during zebrafish gastrulation Pk1 acts, in part, through interaction with the noncanonical Wnt11/Wnt5 pathway to regulate convergent extension cell movements, but is unlikely to simply be a linear component of this pathway. In addition, Pk1 interacts with Tri to mediate posterior migration of branchiomotor neurons, probably independent of the noncanonical Wnt pathway.

Turning heads: Development of vertebrate branchiomotor neurons

“…Furthermore, morpholino-mediated knockdown of zebrafish prickle leads to defects in gastrulation-associated cell movements and tangential migration of nVII neurons (Carreira-Barbosa et al, 2003), as demonstrated previously for trilobite. These results suggest that Trilobite and Prickle function in the same pathway and may modulate environmental cues necessary for initiating and/or maintaining nVII neuron migration.…”

“…A zebrafish homologue of prickle, which encodes a LIM-domain protein component of the Wnt/PCP pathway, is expressed in r4 and r5 in the vicinity of, but not in, migratory nVII neurons (Carreira-Barbosa et al, 2003). Furthermore, morpholino-mediated knockdown of zebrafish prickle leads to defects in gastrulation-associated cell movements and tangential migration of nVII neurons (Carreira-Barbosa et al, 2003), as demonstrated previously for trilobite.…”

“…In contrast to the well-documented roles for environmental cues in nVII neuron migration described above (Studer, 2001;Jessen et al, 2002;Carreira-Barbosa et al, 2003), much less is known about mechanisms that act within nVII neurons to mediate tangential migration. In mouse, genes encoding various axon guidance and cell adhesion molecules are expressed in nVII motor neurons during specific migratory phases (Garel et al, 2000;Muller et al, 2003).…”

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].…”

Role of chromatin remodeling gene Cecr2 in neurulation and inner ear development

“…A ''core'' set of PCP genes was established in Drosophila (Fanto and McNeill, 2004). Homologues in vertebrates include Vangl1/ 2, Frizzled3 and 6, Disheveled1-3, Celsr1, Prickle, Scribbled, PTK7, and Ankrd6 (Schwarz-Romond et al, 2002;Carreira-Barbosa et al, 2003;Curtin et al, 2003;Montcouquiol et al, 2003;Lu et al, 2004;Wang et al, 2006a,b;Torban et al, 2007). Examples of PCP can be observed throughout vertebrate embryogenesis, most notably in the convergent extension (CE) movements required to elongate and shape the neural epithelium during early neurulation, as well as the highly organized epithelium within the cochlear sensory structures (Park and Moon, 2002;Wang et al, 2005).…”