Document Detail

Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during vertebrate development.
MedLine Citation:
PMID:  23533179     Owner:  NLM     Status:  In-Data-Review    
Using zebrafish, we have characterised the function of Protein tyrosine kinase 7 (Ptk7), a transmembrane pseudokinase implicated in Wnt signal transduction during embryonic development and in cancer. Ptk7 is a known regulator of mammalian neural tube closure and Xenopus convergent extension movement. However, conflicting reports have indicated both positive and negative roles for Ptk7 in canonical Wnt/β-catenin signalling. To clarify the function of Ptk7 in vertebrate embryonic patterning and morphogenesis, we generated maternal-zygotic (MZ) ptk7 mutant zebrafish using a zinc-finger nuclease (ZFN) gene targeting approach. Early loss of zebrafish Ptk7 leads to defects in axial convergence and extension, neural tube morphogenesis and loss of planar cell polarity (PCP). Furthermore, during late gastrula and segmentation stages, we observe significant upregulation of β-catenin target gene expression and demonstrate a clear role for Ptk7 in attenuating canonical Wnt/β-catenin activity in vivo. MZptk7 mutants display expanded differentiation of paraxial mesoderm within the tailbud, suggesting an important role for Ptk7 in regulating canonical Wnt-dependent fate specification within posterior stem cell pools post-gastrulation. Furthermore, we demonstrate that a plasma membrane-tethered Ptk7 extracellular fragment is sufficient to rescue both PCP morphogenesis and Wnt/β-catenin patterning defects in MZptk7 mutant embryos. Our results indicate that the extracellular domain of Ptk7 acts as an important regulator of both non-canonical Wnt/PCP and canonical Wnt/β-catenin signalling in multiple vertebrate developmental contexts, with important implications for the upregulated PTK7 expression observed in human cancers.
Madeline Hayes; Mizue Naito; Avais Daulat; Stephane Angers; Brian Ciruna
Related Documents :
20683009 - Epithelial and stromal expression of syndecan-2 in pancreatic carcinoma.
23213449 - Revealing details: whole mount microrna in situ hybridization protocol for zebrafish em...
16516869 - Pentylenetetrazol-induced status epilepticus up-regulates the expression of glucose tra...
24813569 - Sustained behavioral effects of lithium exposure during early development in zebrafish:...
23335859 - Integration of canonical and noncanonical wnt signaling pathways patterns the neuroecto...
2542959 - Proglucagon gene expression is regulated by a cyclic amp-dependent pathway in rat intes...
8683159 - Maintenance of nuclear factor-kappa b/rel and c-myc expression during cd40 ligand rescu...
19211919 - Involvement of redox-sensitive extracellular-regulated kinases in angiotensin ii-induce...
9041129 - Regulation of gene expression in the preimplantation mouse embryo: temporal and spatial...
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  140     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-03-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  1807-18     Citation Subset:  IM    
Program in Developmental & Stem Cell Biology, The Hospital for Sick Children, Toronto, ON, M5G 1X8, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Notch and Nodal control forkhead factor expression in the specification of multipotent progenitors i...
Next Document:  A role for Vg1/Nodal signaling in specification of the intermediate mesoderm.