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Front Cell Dev Biol July 14, 2020; 8 631.
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Heparan Sulfate Proteoglycan Clustering in Wnt Signaling and Dispersal.

Mii Y , Takada S .

Wnt, a family of secreted signal proteins, serves diverse functions in animal development, stem cell systems, and carcinogenesis. Although Wnt is generally considered a morphogen, the mechanism by which Wnt ligands disperse is still debated. Heparan sulfate proteoglycans (HSPGs) are extracellular regulators involved in Wnt ligand dispersal. Drosophila genetics have revealed that HSPGs participate in accumulation and transport of Wnt ligands. Based on these findings, a "restricted diffusion" model, in which Wnt ligands are gradually transferred by repetitive binding and dissociation to HSPGs, has been proposed. Nonetheless, we recently found that HSPGs are not uniformly distributed, but are locally clustered on cell surfaces in Xenopus embryos. HSPGs with N-sulfo-rich HS chains and those with N-acetyl-rich unmodified HS chains form different clusters. Furthermore, endogenous Wnt8 ligands are discretely accumulated in a punctate fashion, colocalized with the N-sulfo-rich clusters. Based on these lines of evidence, here we reconsider the classical view of morphogen spreading controlled by HSPGs.

PubMed ID: 32760727
PMC ID: PMC7371957
Article link: Front Cell Dev Biol

Species referenced: Xenopus
Genes referenced: frzb gpc1 gpc2 gpc4 gpc6 sdc2 wnt3a wnt8a

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References [+] :
Baeg, The Wingless morphogen gradient is established by the cooperative action of Frizzled and Heparan Sulfate Proteoglycan receptors. 2005, Pubmed