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Determination01:51

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During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In contrast, determination...
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PTK7 recruits dsh to regulate neural crest migration.

Iryna Shnitsar1, Annette Borchers

  • 1Department of Developmental Biochemistry, Center for Molecular Physiology of the Brain (CMPB 37077 Goettingen, Germany.

Development (Cambridge, England)
|November 14, 2008
PubMed
Summary

Protein tyrosine kinase 7 (PTK7) recruits dishevelled (dsh) to the plasma membrane, a key step in planar cell polarity (PCP) signaling. This mechanism is crucial for Xenopus neural crest cell migration and vertebrate development.

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Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Signaling

Background:

  • Protein tyrosine kinase 7 (PTK7) is known to regulate planar cell polarity (PCP) signaling in vertebrates.
  • The precise molecular mechanism by which PTK7 functions in PCP signaling remains largely unknown.
  • PTK7's role in cellular processes beyond neural tube and inner ear development requires further elucidation.

Purpose of the Study:

  • To investigate the signaling mechanism of PTK7 in the context of Xenopus neural crest cell migration.
  • To define the intersection of PTK7 with the non-canonical Wnt signaling pathway that governs PCP.
  • To elucidate how PTK7 regulates cell movements during vertebrate development.

Main Methods:

  • Utilized Xenopus ectodermal explants for in vitro assays to study PTK7-dishevelled (dsh) interactions.
  • Employed immunoprecipitation experiments to confirm protein complex formation.
  • Analyzed Xenopus embryos and transplanted neural crest cells to assess in vivo PTK7 function in migration.

Main Results:

  • Demonstrated that PTK7 recruits dishevelled (dsh) to the plasma membrane in a manner dependent on dsh's PDZ domain and PTK7's kinase domain.
  • Showed that endogenous PTK7 is essential for frizzled7-mediated dsh localization and forms a complex with dsh and frizzled7.
  • Confirmed that PTK7 loss-of-function and specific PTK7/dsh mutants inhibit Xenopus neural crest cell migration in vivo.

Conclusions:

  • PTK7 plays a critical role in regulating Xenopus neural crest cell migration by recruiting dsh to the cell membrane.
  • Established a molecular link between PTK7 and the PCP pathway, specifically through dsh localization.
  • Provided evidence for PTK7's function in coordinating cell movements essential for vertebrate development.