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.
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6 December 2021
Article|
September 30 2021
Glypican 4 mediates Wnt transport between germ layers via signaling filopodia
Bo Hu
,
Bo Hu
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Juan J. Rodriguez
,
Juan J. Rodriguez
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Anurag Kakkerla Balaraju,
Anurag Kakkerla Balaraju
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Yuanyuan Gao,
Yuanyuan Gao
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Nhan T. Nguyen,
Nhan T. Nguyen
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Heston Steen,
Heston Steen
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Saeb Suhaib
,
Saeb Suhaib
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Songhai Chen,
Songhai Chen
2
Department of Neuroscience and Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA
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Fang Lin
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Correspondence to Fang Lin: fang-lin@uiowa.edu
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1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Juan J. Rodriguez
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Anurag Kakkerla Balaraju
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Yuanyuan Gao
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Nhan T. Nguyen
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Heston Steen
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Saeb Suhaib
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Songhai Chen
2
Department of Neuroscience and Pharmacology, Carver College of Medicine, The University of Iowa, Iowa City, IA
1
Department of Anatomy and Cell Biology, Carver College of Medicine, The University of Iowa, Iowa City, IA
Correspondence to Fang Lin: fang-lin@uiowa.edu
Received:
September 14 2020
Revision Received:
July 18 2021
Accepted:
September 08 2021
Online Issn: 1540-8140
Print Issn: 0021-9525
Funding
Funder(s):
National Science Foundation
- Award Id(s): IOS-1354457
Funder(s):
National Institutes of Health
- Award Id(s): 1R56DK123610-01,R01 CA207889
Funder(s):
Department of Defense
- Award Id(s): BC151478
© 2021 Hu et al.
2021
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Cell Biol (2021) 220 (12): e202009082.
Article history
Received:
September 14 2020
Revision Received:
July 18 2021
Accepted:
September 08 2021
Connected Content
Citation
Bo Hu, Juan J. Rodriguez, Anurag Kakkerla Balaraju, Yuanyuan Gao, Nhan T. Nguyen, Heston Steen, Saeb Suhaib, Songhai Chen, Fang Lin; Glypican 4 mediates Wnt transport between germ layers via signaling filopodia. J Cell Biol 6 December 2021; 220 (12): e202009082. doi: https://doi.org/10.1083/jcb.202009082
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