PUBLICATION

Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain

Authors
Powell, G.T., Faro, A., Zhao, Y., Stickney, H., Novellasdemunt, L., Henriques, P., Gestri, G., Redhouse White, E., Ren, J., Lu, W., Young, R.M., Hawkins, T.A., Cavodeassi, F., Schwarz, Q., Dreosti, E., Raible, D.W., Li, V.S.W., Wright, G.J., Jones, E.Y., Wilson, S.W.
ID
ZDB-PUB-240503-1
Date
2024
Source
Science (New York, N.Y.)   384: 573579573-579 (Journal)
Registered Authors
Cavodeassi, Florencia, Dreosti, Elena, Faro, Ana, Gestri, Gaia, Hawkins, Tom, Henriques, Pedro, Powell, Gareth, Raible, David, Wilson, Steve, Wright, Gavin J., Young, Rodrigo
Keywords
none
MeSH Terms
  • Animals
  • Zebrafish*/genetics
  • Loss of Function Mutation
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism
  • Wnt Signaling Pathway*
  • Brain/metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6/genetics
  • Low Density Lipoprotein Receptor-Related Protein-6/metabolism
  • Receptors, Wnt/genetics
  • Receptors, Wnt/metabolism
  • Frizzled Receptors/genetics
  • Frizzled Receptors/metabolism
  • Neurogenesis*
  • Neurons*/metabolism
  • Habenula*/embryology
  • Habenula*/metabolism
  • Zebrafish Proteins*/genetics
  • Zebrafish Proteins*/metabolism
(all 19)
PubMed
38696577 Full text @ Science
Abstract
Neurons on the left and right sides of the nervous system often show asymmetric properties, but how such differences arise is poorly understood. Genetic screening in zebrafish revealed that loss of function of the transmembrane protein Cachd1 resulted in right-sided habenula neurons adopting left-sided identity. Cachd1 is expressed in neuronal progenitors, functions downstream of asymmetric environmental signals, and influences timing of the normally asymmetric patterns of neurogenesis. Biochemical and structural analyses demonstrated that Cachd1 can bind simultaneously to Lrp6 and Frizzled family Wnt co-receptors. Consistent with this, lrp6 mutant zebrafish lose asymmetry in the habenulae, and epistasis experiments support a role for Cachd1 in modulating Wnt pathway activity in the brain. These studies identify Cachd1 as a conserved Wnt receptor-interacting protein that regulates lateralized neuronal identity in the zebrafish brain.
Genes / Markers
Figures
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Human Disease / Model
No data available
Sequence Targeting Reagents
Target Reagent Reagent Type
cachd1MO1-cachd1MRPHLNO
cachd1MO2-cachd1MRPHLNO
lrp6CRISPR1-lrp6CRISPR
lrp6CRISPR2-lrp6CRISPR
1 - 4 of 4
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Fish
No data available
Antibodies
Orthology
No data available
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
GFPEFGGFP
1 - 2 of 2
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Mapping
No data available