Glypican 4 mediates Wnt transport between germ layers via signaling filopodia

Bo Hu; Juan J Rodriguez; Anurag Kakkerla Balaraju; Yuanyuan Gao; Nhan T Nguyen; Heston Steen; Saeb Suhaib; Songhai Chen; Fang Lin

doi:10.1083/jcb.202009082

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Glypican 4 mediates Wnt transport between germ layers via signaling filopodia

Journal article

Open access

Peer reviewed

Glypican 4 mediates Wnt transport between germ layers via signaling filopodia

Bo Hu, Juan J Rodriguez, Anurag Kakkerla Balaraju, Yuanyuan Gao, Nhan T Nguyen, Heston Steen, Saeb Suhaib, Songhai Chen and Fang Lin

The Journal of cell biology, Vol.220(12), p.1

12/06/2021

DOI: 10.1083/jcb.202009082

PMCID: PMC8488972

PMID: 34591076

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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.

Signal Transduction

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

Wnt Proteins - metabolism

Wnt-5a Protein - metabolism

Zebrafish

Zebrafish Proteins - metabolism

Details

Title: Subtitle: Glypican 4 mediates Wnt transport between germ layers via signaling filopodia
Creators: Bo Hu - University of Iowa
Juan J Rodriguez - University of Iowa
Anurag Kakkerla Balaraju - Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Yuanyuan Gao - University of Iowa
Nhan T Nguyen - Roy J. and Lucille A. Carver College of Medicine
Heston Steen - Roy J. and Lucille A. Carver College of Medicine
Saeb Suhaib - Roy J. and Lucille A. Carver College of Medicine
Songhai Chen - University of Iowa
Fang Lin - Roy J. and Lucille A. Carver College of Medicine
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.220(12), p.1
DOI: 10.1083/jcb.202009082
PMID: 34591076
PMCID: PMC8488972
NLM abbreviation: J Cell Biol
ISSN: 0021-9525
eISSN: 1540-8140
Grant note: R01 CA207889 / NCI NIH HHS 1R56DK123610-01 / NIH HHS R56 DK123610 / NIDDK NIH HHS
Language: English
Date published: 12/06/2021
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984288754102771

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