ZFIN ID: ZDB-PUB-201126-9
Wnt3 distribution in the zebrafish brain is determined by expression, diffusion and multiple molecular interactions
Veerapathiran, S., Teh, C., Zhu, S., Kartigayen, I., Korzh, V., Matsudaira, P.T., Wohland, T.
Date: 2020
Source: eLIFE   9: (Journal)
Registered Authors: Korzh, Vladimir, Teh, Cathleen, Veerapathiran, Sapthaswaran, Wohland, Thorsten
Keywords: developmental biology, zebrafish
MeSH Terms:
  • Animals
  • Animals, Genetically Modified
  • Brain/embryology
  • Brain/metabolism*
  • Embryo, Nonmammalian
  • Fluorescence Recovery After Photobleaching
  • Frizzled Receptors/genetics
  • Frizzled Receptors/metabolism
  • Gene Expression Regulation, Developmental/physiology*
  • Heparan Sulfate Proteoglycans/metabolism
  • Low Density Lipoprotein Receptor-Related Protein-5/genetics
  • Low Density Lipoprotein Receptor-Related Protein-5/metabolism
  • Microscopy, Confocal
  • Protein Binding
  • Wnt3 Protein/genetics
  • Wnt3 Protein/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 33236989 Full text @ Elife
Wnt3 proteins are lipidated and glycosylated, secreted signaling molecules that play an important 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 distribution 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 photobleaching. 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), using 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.