title: 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)/wnt5 phenotypes and suppresses the ability of Wnt11 to rescue the slb phenotype. 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 pk1 interacts 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.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.
authors.forename: Filipa
authors.initials: F
authors.lastname: Carreira-Barbosa
authors.forename: Miguel L
authors.initials: ML
authors.lastname: Concha
authors.forename: Masaki
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Naoto
authors.initials: N
authors.lastname: Ueno
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Wilson
authors.forename: Masazumi
authors.initials: M
authors.lastname: Tada
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005775:Gastrula / Q000378:metabolism*; D060588:LIM Domain Proteins; D008565:Membrane Proteins / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C121600:pk protein, Drosophila; C491759:vangl2 protein, zebrafish; C094522:wnt8b protein, zebrafish