PUBLICATION

Glypican 4 mediates Wnt transport between germ layers via signaling filopodia

Authors
Hu, B., Rodriguez, J.J., Kakkerla Balaraju, A., Gao, Y., Nguyen, N.T., Steen, H., Suhaib, S., Chen, S., Lin, F.
ID
ZDB-PUB-211001-9
Date
2021
Source
The Journal of cell biology   220(12): (Journal)
Registered Authors
Lin, Fang
Keywords
none
MeSH Terms
  • Actins/metabolism
  • Animals
  • Embryo, Nonmammalian/metabolism
  • Endoderm/metabolism
  • Germ Layers/embryology
  • Germ Layers/metabolism*
  • Glycosylphosphatidylinositols/metabolism
  • Green Fluorescent Proteins/metabolism
  • Heparan Sulfate Proteoglycans/metabolism*
  • JNK Mitogen-Activated Protein Kinases
  • Mesoderm/embryology
  • Mesoderm/metabolism
  • Protein Transport
  • Pseudopodia/metabolism*
  • Signal Transduction*
  • Wnt Proteins/metabolism*
  • Wnt-5a Protein/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed
34591076 Full text @ J. Cell Biol.
Abstract
Glypicans influence signaling pathways by regulating morphogen trafficking and reception. However, the underlying mechanisms in vertebrates are poorly understood. In zebrafish, Glypican 4 (Gpc4) is required for convergence and extension (C&E) of both the mesoderm and endoderm. Here, we show that transgenic expression of GFP-Gpc4 in the endoderm of gpc4 mutants rescued C&E defects in all germ layers. The rescue of mesoderm was likely mediated by Wnt5b and Wnt11f2 and depended on signaling filopodia rather than on cleavage of the Gpc4 GPI anchor. Gpc4 bound both Wnt5b and Wnt11f2 and regulated formation of the filopodia that transport Wnt5b and Wnt11f2 to neighboring cells. Moreover, this rescue was suppressed by blocking signaling filopodia that extend from endodermal cells. Thus, GFP-Gpc4-labeled protrusions that emanated from endodermal cells transported Wnt5b and Wnt11f2 to other germ layers, rescuing the C&E defects caused by a gpc4 deficiency. Our study reveals a new mechanism that could explain in vivo morphogen distribution involving Gpc4.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping