Lrp6 is required for convergent extension during Xenopus gastrulation.
Wnt signaling regulates beta-catenin-mediated gene transcription and planar cell polarity (PCP). The Wnt co-receptor, Lrp6, is required for signaling along the beta-catenin arm. We show that Lrp6 downregulation (by morpholino injection) or overexpression in Xenopus embryos disrupts convergent extension, a hallmark feature of Wnt/PCP components. In embryos with decreased Lrp6 levels, cells of the dorsal marginal zone (DMZ), which undergoes extensive cellular rearrangements during gastrulation, exhibit decreased length:width ratios, decreased migration, and increased numbers of transient cytoplasmic protrusions. We show that Lrp6 opposes Wnt11 activity and localizes to the posterior edge of migrating DMZ cells and that Lrp6 downregulation enhances cortical and nuclear localization of Dsh and phospho-JNK, respectively. Taken together, these data suggest that Lrp6 inhibits Wnt/PCP signaling. Finally, we identify the region of the Lrp6 protein with Wnt/PCP activity to a stretch of 36 amino acids, distinct from regions required for Wnt/beta-catenin signaling. We propose a model in which Lrp6 plays a critical role in the switch from Wnt/PCP to Wnt/beta-catenin signaling.
Tahinci
Emilios
E
Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Thorne
Curtis A
CA
Franklin
Jeffrey L
JL
Salic
Adrian
A
Christian
Kelly M
KM
Lee
Laura A
LA
Coffey
Robert J
RJ
Lee
Ethan
E
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D019521:Body Patterning / Q000235:genetics*; D016764:Cell Polarity / Q000235:genetics*; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian; D054262:Gastrulation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008648:Mesoderm / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics; D014018:Tissue Distribution; D051153:Wnt Proteins / Q000235:genetics; D014981:Xenopus / Q000196:embryology* / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000502:physiology
C555475:LRP6 protein, human; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D011973:Receptors, LDL; D051153:Wnt Proteins; D051176:beta Catenin