RT Journal Article
SR Electronic
T1 Wnt3 distribution in the zebrafish brain is determined by expression, diffusion and multiple molecular interactions
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.29.124560
DO 10.1101/2020.05.29.124560
A1 Sapthaswaran Veerapathiran
A1 Cathleen Teh
A1 Shiwen Zhu
A1 Indira Kartigayen
A1 Vladimir Korzh
A1 Paul T. Matsudaira
A1 Thorsten Wohland
YR 2020
UL http://biorxiv.org/content/early/2020/05/30/2020.05.29.124560.abstract
AB 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 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), 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.Competing Interest StatementThe authors have declared no competing interest.