title: PAPC and the Wnt5a/Ror2 pathway control the invagination of the otic placode in Xenopus.
abstract: BACKGROUND
  Paraxial protocadherin (PAPC) plays a crucial role in morphogenetic movements during gastrulation and somitogenesis in mouse, zebrafish and Xenopus. PAPC influences cell-cell adhesion mediated by C-Cadherin. A putative direct adhesion activity of PAPC is discussed. PAPC also promotes cell elongation, tissue separation and coordinates cell mass movements. In these processes the signaling function of PAPC in activating RhoA/JNK and supporting Wnt-11/PCP by binding to frizzled 7 (fz7) is important.
  
  
  RESULTS
  Here we demonstrate by loss of function experiments in Xenopus embryos that PAPC regulates another type of morphogenetic movement, the invagination of the ear placode. Knockdown of PAPC by antisense morpholinos results in deformation of the otic vesicle without altering otocyst marker expression. Depletion of PAPC could be rescued by full-length PAPC, constitutive active RhoA and by the closely related PCNS but not by classical cadherins. Also the cytoplasmic deletion mutant M-PAPC, which influences cell adhesion, does not rescue the PAPC knockdown. Interestingly, depletion of Wnt5a or Ror2 which are also expressed in the otocyst phenocopies the PAPC morphant phenotype.
  
  
  CONCLUSIONS
  PAPC signaling via RhoA and Wnt5a/Ror2 activity are required to keep cells aligned in apical-basal orientation during invagination of the ear placode. Since neither the cytoplasmic deletion mutant M-PAPC nor a classical cadherin is able to rescue loss of PAPC we suggest that the signaling function of the protocadherin rather than its role as modulator of cell-cell adhesion is required during invagination of the ear placode.
authors.affiliation: Karlsruhe Institute of Technology, Department of Cell and Developmental Biology, Karlsruhe, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Jung
authors.forename: Almut
authors.initials: A
authors.lastname: Köhler
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schambony
authors.forename: Doris
authors.initials: D
authors.lastname: Wedlich
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D000072261:Dishevelled Proteins; D004423:Ear / Q000002:abnormalities / Q000033:anatomy & histology / Q000196:embryology*; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology; D055785:Gene Knockdown Techniques; D009024:Morphogenesis / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000235:genetics; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D000091363:Protocadherins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000033:anatomy & histology* / Q000196:embryology* / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D000072261:Dishevelled Proteins; C492040:Fzd7 protein, Xenopus; D016376:Oligonucleotides, Antisense; C117635:Pcdh8 protein, Xenopus; D010750:Phosphoproteins; D000091363:Protocadherins; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C085096:Wnt5a protein, Xenopus; D029867:Xenopus Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D020742:rhoA GTP-Binding Protein