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Development January 1, 2014; 141 (2): 410-21.

PTK7 modulates Wnt signaling activity via LRP6.

Bin-Nun N , Lichtig H , Malyarova A , Levy M , Elias S , Frank D .

Protein tyrosine kinase 7 (PTK7) is a transmembrane protein expressed in the developing Xenopus neural plate. PTK7 regulates vertebrate planar cell polarity (PCP), controlling mesodermal and neural convergent-extension (CE) cell movements, neural crest migration and neural tube closure in vertebrate embryos. Besides CE phenotypes, we now show that PTK7 protein knockdown also inhibits Wnt/β-catenin activity. Canonical Wnt signaling caudalizes the neural plate via direct transcriptional activation of the meis3 TALE-class homeobox gene, which subsequently induces neural CE. PTK7 controls meis3 gene expression to specify posterior tissue and downstream PCP activity. Furthermore, PTK7 morphants phenocopy embryos depleted for Wnt3a, LRP6 and Meis3 proteins. PTK7 protein depletion inhibits embryonic Wnt/β-catenin signaling by strongly reducing LRP6 protein levels. LRP6 protein positively modulates Wnt/β-catenin, but negatively modulates Wnt/PCP activities. The maintenance of high LRP6 protein levels by PTK7 triggers PCP inhibition. PTK7 and LRP6 proteins physically interact, suggesting that PTK7 stabilization of LRP6 protein reciprocally regulates both canonical and noncanonical Wnt activities in the embryo. We suggest a novel role for PTK7 protein as a modulator of LRP6 that negatively regulates Wnt/PCP activity.

PubMed ID: 24353057
Article link: Development

Species referenced: Xenopus laevis
Genes referenced: acss2.2 atf2 ctnnb1 dvl1 dvl2 egr2 fzd7 hoxb3 hoxd1 lrp6 meis3 myc nodal3.1 nodal3.2 nog nrp1 ptk7 sia1 snai2 tub tubb2b wnt11 wnt3a
Antibodies: HA Ab3 Myc Ab6 Tuba4b Ab2 VSV-G Ab1
Morpholinos: meis3 MO1 ptk7 MO1 ptk7 MO2 ptk7 MO3

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