Chondroitin sulfate proteoglycan 4 regulates zebrafish body axis organization via Wnt/planar cell polarity pathway

Pericellular and extracellular proteoglycans play an important role in modulating morphogen gradients and signal transductions. Chondroitin sulfate proteoglycan 4 (Cspg4) is a membrane spanning proteoglycan expressed in immature progenitor cells and cancer cells. Cspg4 participates in cellular event...

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Bibliographic Details
Published in:PloS one 2020-04, Vol.15 (4), p.e0230943-e0230943
Main Authors: Lee, Yen-Hua, Kawakami, Koichi, HuangFu, Wei-Chun, Liu, I-Hsuan
Format: Article
Language:English
Subjects:
Animal genetic engineering
Animal sciences
Antigens
Binding sites
Biology and Life Sciences
Cancer cells
Cell adhesion & migration
Cell division
Cell growth
Cell proliferation
Cells (biology)
Cellular signal transduction
Chondroitin
Chondroitin sulfate
Cloning
Coinjection
Collagen
Danio rerio
Developmental biology
EDTA
Embryo
Embryogenesis
Embryonic development
Embryonic growth stage
Embryos
Extracellular matrix
Fertilization
Gastrulation
Gene expression
Growth factors
Heparan sulfate
Hybridization
Laboratories
Medicine and Health Sciences
Melanoma
Messenger RNA
mRNA
Mutants
Overexpression
Physical Sciences
Plasmids
Polarity
Progenitor cells
Proteins
Proteoglycans
Research and Analysis Methods
RNA
Signal transduction
Stem cells
Sulfates
Wnt protein
Zebrafish
Zoology
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Summary:Pericellular and extracellular proteoglycans play an important role in modulating morphogen gradients and signal transductions. Chondroitin sulfate proteoglycan 4 (Cspg4) is a membrane spanning proteoglycan expressed in immature progenitor cells and cancer cells. Cspg4 participates in cellular events such as proliferation, migration and signal transduction, and these events are generally important for embryo development. In this study, we characterized Cspg4 for its roles in zebrafish embryonic development. Our results demonstrated that cspg4 was maternally expressed from 0 to 3 hours post fertilization (hpf) and expressed in the anterior and posterior embryo end after 9 hpf. Knocking-down cspg4 resulted in a shorter anterior-posterior axis than control embryo, which could be rescued by co-injecting wnt11 mRNA suggesting that Cspg4 regulates body axis organization through modulating the Wnt/planar cell polarity signaling pathway. In addition, overexpressing cspg4 caused cyclopia. The Cspg4 transmembrane domain mutant embryo phenocopied the global over-expression of cspg4 mRNA and led to cyclopia with a very low penetrance. Our results demonstrated that the quantitatively and spatially accurate distribution of Cspg4 is critical for body axis and midline development during gastrulation.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0230943