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PKCgamma regulates syndecan-2 inside-out signaling during xenopus left-right development

Kenneth L Kramer1, Janet E Barnette, H Joseph Yost

  • 1Center for Children, Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City 84112, USA.

Cell
|January 1, 2003
PubMed

Insights

Protein kinase C gamma (PKCgamma) controls syndecan-2 phosphorylation in right ectodermal cells, a crucial step for left-right (LR) development. This phosphorylation is essential for asymmetric gene expression and organ orientation during early development.

Area of Science:

  • Developmental Biology
  • Cell Signaling
  • Molecular Biology

Background:

  • The transmembrane proteoglycan syndecan-2 plays a non-autonomous role in left-right (LR) developmental patterning.
  • The precise molecular mechanism by which syndecan-2 regulates LR asymmetry, including gene expression and organ orientation, remains largely unknown.
  • LR development is a complex process involving asymmetric signaling early in embryonic development.

Purpose of the Study:

  • To investigate the role of protein kinase C gamma (PKCgamma) in the regulation of syndecan-2 during left-right (LR) development.
  • To elucidate the mechanism by which syndecan-2 phosphorylation influences LR asymmetric gene expression and organ orientation.
  • To identify the earliest molecular events in LR development mediated by cell-cell interactions.

Main Methods:

  • Utilized animal cap explants to study ectodermal cell interactions with migrating mesoderm.
  • Investigated the phosphorylation status of syndecan-2 in right and left ectodermal cells.
  • Examined the role of PKCgamma in mediating syndecan-2 phosphorylation.
  • Assessed the necessity of both phosphorylated and non-phosphorylated syndecan-2 states for normal LR development.

Main Results:

  • Demonstrated that protein kinase C gamma (PKCgamma) mediates the phosphorylation of syndecan-2's cytoplasmic domain specifically in right animal cap ectodermal cells.
  • Showed that both phosphorylated syndecan-2 (in right cells) and non-phosphorylated syndecan-2 (in left cells) are essential for normal LR development.
  • Established that this ectodermal-mesodermal cell contact and syndecan-2 phosphorylation occur early in gastrulation, preceding monocilia appearance.
  • Concluded that PKCgamma regulates syndecan-2 phosphorylation, impacting inside-out signaling to adjacent cells.

Conclusions:

  • PKCgamma is a key regulator of syndecan-2 phosphorylation in right ectodermal cells during early LR development.
  • Syndecan-2 phosphorylation status, modulated by PKCgamma, is critical for establishing LR asymmetry.
  • This study reveals an early, cell-contact-dependent mechanism involving syndecan-2 and PKCgamma in LR patterning, preceding known later events like monocilia formation.

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