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
- Keywords
- none
- MeSH Terms
-
- Animals
- Brain/metabolism
- Frizzled Receptors/genetics
- Frizzled Receptors/metabolism
- Habenula*/embryology
- Habenula*/metabolism
- Loss of Function Mutation
- Low Density Lipoprotein Receptor-Related Protein-6/genetics
- Low Density Lipoprotein Receptor-Related Protein-6/metabolism
- Membrane Proteins/genetics
- Membrane Proteins/metabolism
- Neurogenesis*
- Neurons*/metabolism
- Receptors, Wnt/genetics
- Receptors, Wnt/metabolism
- Wnt Signaling Pathway*
- Zebrafish*/genetics
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 38696577 Full text @ Science
Citation
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. (2024) Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain. Science (New York, N.Y.). 384:573579573-579.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping