title: Lpp is involved in Wnt/PCP signaling and acts together with Scrib to mediate convergence and extension movements during zebrafish gastrulation.
abstract: The zyxin-related LPP protein is localized at focal adhesions and cell-cell contacts and is involved in the regulation of smooth muscle cell migration. A known interaction partner of LPP in human is the tumor suppressor protein SCRIB. Knocking down scrib expression during zebrafish embryonic development results in defects of convergence and extension (C&E) movements, which occur during gastrulation and mediate elongation of the anterior-posterior body axis. Mediolateral cell polarization underlying C&E is regulated by a noncanonical Wnt signaling pathway constituting the vertebrate planar cell polarity (PCP) pathway. Here, we investigated the role of Lpp during early zebrafish development. We show that morpholino knockdown of lpp results in defects of C&E, phenocopying noncanonical Wnt signaling mutants. Time-lapse analysis associates the defective dorsal convergence movements with a reduced ability to migrate along straight paths. In addition, expression of Lpp is significantly reduced in Wnt11 morphants and in embryos overexpressing Wnt11 or a dominant-negative form of Rho kinase 2, which is a downstream effector of Wnt11, suggesting that Lpp expression is dependent on noncanonical Wnt signaling. Finally, we demonstrate that Lpp interacts with the PCP protein Scrib in zebrafish, and that Lpp and Scrib cooperate for the mediation of C&E.
authors.affiliation: Laboratory for Molecular Oncology, Department of Human Genetics, K.U. Leuven, Leuven, Belgium.
authors.forename: Hilke B V K
authors.initials: HB
authors.lastname: Vervenne
authors.forename: Koen R M O
authors.initials: KR
authors.lastname: Crombez
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lambaerts
authors.forename: Lara
authors.initials: L
authors.lastname: Carvalho
authors.forename: Mathias
authors.initials: M
authors.lastname: Köppen
authors.forename: Carl-Philipp
authors.initials: CP
authors.lastname: Heisenberg
authors.forename: Wim J M
authors.initials: WJ
authors.lastname: Van de Ven
authors.forename: Marleen M R
authors.initials: MM
authors.lastname: Petit
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D054262:Gastrulation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008667:Metalloproteins / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C530880:Lpp protein, zebrafish; D008565:Membrane Proteins; D008667:Metalloproteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C502707:scrib protein, zebrafish