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Wnt3 distribution in the zebrafish brain is determined by expression, diffusion and multiple molecular interactions

Authors: 
Veerapathiran S, Teh C, Zhu S, Kartigayen I, Korzh V, Matsudaira PT, Wohland T
Citation: 
bioRxiv. 2020;[preprint] doi:10.1101/2020.05.29.124560
Abstract: 
Wnt3 proteins are lipidated and glycosylated, secreted signaling molecules that play an im-portant role in zebrafish neural patterning and brain development. However, the transport mechanism of lipid-modified Wnts through the hydrophilic extracellular environment for long-range action remains unresolved. Here, we determine how Wnt3 accomplishes long-range dis-tribution in the zebrafish brain. First, we characterize the Wnt3-producing source and Wnt3-receiving target regions. Subsequently, we analyze Wnt3 mobility at different length scales by fluorescence correlation spectroscopy and fluorescence recovery after photo-bleaching. We demonstrate that Wnt3 spreads extracellularly and interacts with heparan sulfate proteoglycans (HSPG). We then determine the binding affinity of Wnt3 to its receptor, Frizzled1 (Fzd1), us-ing fluorescence cross-correlation spectroscopy, and show that the co-receptor, low-density lipoprotein receptor-related protein 5 (Lrp5), is required for Wnt3-Fzd1 interaction. Our results are consistent with the extracellular distribution of Wnt3 by a diffusive mechanism that is modified by tissue morphology, interactions with HSPG and Lrp5-mediated receptor binding, to regulate zebrafish brain development.
Epub: 
Not Epub
Organism or Cell Type: 
zebrafish
Delivery Method: 
microinjection