Wnt-5A/Ror2 regulate expression of XPAPC through an alternative noncanonical signaling pathway.
XWnt-5A, a member of the nontransforming Wnt-5A class of Wnt ligands, is required for convergent extension movements in Xenopus embryos. XWnt-5A knockdown phenocopies paraxial protocadherin (XPAPC) loss of function: involuted mesodermal cells fail to align mediolaterally, which results in aberrant movements and a selective inhibition of constriction. XWnt-5A depletion was rescued by coinjection of XPAPC RNA, indicating that XWnt-5A acts upstream of XPAPC. XWnt-5A, but not XWnt-11, stimulates XPAPC expression independent of the canonical Wnt/beta-catenin pathway. We show that transcriptional regulation of XPAPC by XWnt-5A requires the receptor tyrosine kinase Ror2. XWnt-5A/Xror2 signal through PI3 kinase and cdc42 to activate the JNK signaling cascade with the transcription factors ATF2 and c-jun. The Wnt-5A/Ror2 pathway represents an alternative, distinct branch of noncanonical Wnt signaling that controls gene expression and is required in the regulation of convergent extension movements in Xenopus gastrulation.
Schambony
Alexandra
A
Universitaet Karlsruhe (TH), Zoologisches Institut II, Kaiserstrasse 12, D-76128 Karlsruhe, Germany. schambony@zi2.uka.de
Wedlich
Doris
D
D016475:3T3 Cells; D000818:Animals; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D016764:Cell Polarity; D048430:Cell Shape; D004625:Embryo, Nonmammalian / Q000166:cytology; D018507:Gene Expression Regulation, Developmental; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000091363:Protocadherins; D015398:Signal Transduction; D014158:Transcription, Genetic; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D015820:Cadherins; D048031:JNK Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000091363:Protocadherins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins; D020764:cdc42 GTP-Binding Protein; C117635:Pcdh8 protein, Xenopus; C085096:Wnt5a protein, Xenopus