PUBLICATION

Glypican 4 regulates planar cell polarity of endoderm cells by controlling the localization of Cadherin 2

Authors
Balaraju, A.K., Hu, B., Rodriguez, J.J., Murry, M., Lin, F.
ID
ZDB-PUB-210705-4
Date
2021
Source
Development (Cambridge, England)   148(14): (Journal)
Registered Authors
Lin, Fang
Keywords
Cadherin 2, Endoderm C&E, Glypican 4, Planar cell polarity, Zebrafish
MeSH Terms
  • Animals
  • Cadherins/metabolism*
  • Cell Polarity/physiology*
  • Endoderm/metabolism*
  • Gastrulation
  • Gene Expression Regulation, Developmental
  • Glypicans/metabolism*
  • Heparan Sulfate Proteoglycans/metabolism
  • Morphogenesis
  • Wnt Proteins/metabolism
  • Wnt Signaling Pathway
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism*
  • rab5 GTP-Binding Proteins
PubMed
34131730 Full text @ Development
Abstract
Non-canonical Wnt/Planar Cell Polarity (Wnt/PCP) signaling has been implicated in endoderm morphogenesis. However, the underlying cellular and molecular mechanisms of this process are unclear. We found that during convergence and extension (C&E) in zebrafish, gut endodermal cells are polarized mediolaterally, with GFP-Vangl2 enriched at the anterior edges. Endoderm cell polarity is lost, and intercalation is impaired, in the absence of glypican 4 (gpc4), a heparan-sulfate proteoglycan that promotes Wnt/PCP signaling, suggesting that this signaling is required for endodermal cell polarity. Live imaging revealed that endoderm C&E is accomplished by polarized cell protrusions and junction remodeling, which are impaired in gpc4-deficient endodermal cells. Furthermore, in the absence of gpc4, Cadherin 2 expression on the endodermal cell surface is increased due to impaired Rab5c-mediated endocytosis, which partially accounts for the endodermal defects in these mutants.These findings indicate that Gpc4 regulates endodermal planar cell polarity during endoderm C&E by influencing localization of Cadherin 2. Thus, our study uncovers a new mechanism by which Gpc4 regulates planar cell polarity and reveals the role of Wnt/PCP signaling in endoderm morphogenesis.
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