title: Zebrafish prickle, a modulator of noncanonical Wnt/Fz signaling, regulates gastrulation movements.
abstract: In addition to the canonical Wnt/beta-catenin signaling pathway, at least two noncanonical Wnt/Fz pathways have been described: the planar cell polarity (PCP) pathway in Drosophila [1] and the Wnt/calcium pathway in vertebrate embryos [2]. Recent work suggests that a vertebrate pathway homologous to the PCP pathway acts to regulate the convergent extension movements of gastrulation [3-7]. To further test this hypothesis, we have identified two zebrafish homologs of the Drosophila PCP gene prickle (pk) [8], both of which show discrete and dynamic expression patterns during gastrulation. Both gain and loss of pk1 function cause defects in convergent extension. Pk1 localizes to both the cytoplasm and the cell membrane, and its normal localization is partially dependent on its C-terminal prenylation motif. At the cell membrane, Pk1 is frequently localized asymmetrically around the cell and can colocalize with the signaling molecule Dishevelled (Dsh). In overexpression assays, Pk1 is able to activate AP-1-mediated transcription and inhibit activation of Wnt/beta-catenin signaling. Like noncanonical Wnts [9-10], overexpression of Pk1 increases the frequency of calcium transients in zebrafish blastulae. Our results support the idea that a vertebrate PCP pathway regulates gastrulation movements and suggest that there is overlap between the PCP and Wnt/calcium pathways.
authors.affiliation: Department of Pharmacology, Center for Developmental Biology, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, WA 98195, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Veeman
authors.forename: Diane C
authors.initials: DC
authors.lastname: Slusarski
authors.forename: Ajamete
authors.initials: A
authors.lastname: Kaykas
authors.forename: Sarah Hallagan
authors.initials: SH
authors.lastname: Louie
authors.forename: Randall T
authors.initials: RT
authors.lastname: Moon
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins / Q000235:genetics*; D051157:Frizzled Receptors; D005775:Gastrula / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006023:Glycoproteins / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D060588:LIM Domain Proteins; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology* / Q000502:physiology; D029961:Zebrafish Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D006023:Glycoproteins; D060588:LIM Domain Proteins; D010750:Phosphoproteins; D011506:Proteins; D051153:Wnt Proteins; C092568:Wnt11 protein, zebrafish; D029961:Zebrafish Proteins; C000606588:dsh protein, Drosophila; C121600:pk protein, Drosophila