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

Gareth T Powell; Ana Faro; Yuguang Zhao; Heather Stickney; Laura Novellasdemunt; Pedro Henriques; Gaia Gestri; Esther Redhouse White; Jingshan Ren; Weixian Lu; Rodrigo M Young; Thomas A Hawkins; Florencia Cavodeassi; Quenten Schwarz; Elena Dreosti; David W Raible; Vivian S W Li; Gavin J Wright; E Yvonne Jones; Stephen W Wilson

doi:10.1126/science.ade6970

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

Gareth T Powell, Ana Faro, Yuguang Zhao, Heather Stickney, Laura Novellasdemunt, Pedro Henriques, Gaia Gestri, Esther Redhouse White, Jingshan Ren, Weixian Lu, Rodrigo M Young, Thomas A Hawkins, Florencia Cavodeassi, Quenten Schwarz, Elena Dreosti, David W Raible, Vivian S W Li, Gavin J Wright, E Yvonne Jones, Stephen W Wilson

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	573-579
Number of pages	7
Journal	Science (New York, N.Y.)
Volume	384
Issue number	6695
DOIs	https://doi.org/10.1126/science.ade6970
Publication status	Published - 3 May 2024

Keywords

Animals
Frizzled Receptors/metabolism
Habenula/metabolism
Loss of Function Mutation
Low Density Lipoprotein Receptor-Related Protein-6/metabolism
Membrane Proteins/metabolism
Neurogenesis
Neurons/metabolism
Receptors, Wnt/metabolism
Wnt Signaling Pathway
Zebrafish/embryology
Zebrafish Proteins/metabolism
Calcium Channels/genetics

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10.1126/science.ade6970Licence: CC BY

Cite this

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(6695), 573-579. https://doi.org/10.1126/science.ade6970

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title = "Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain",

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.",

keywords = "Animals, Frizzled Receptors/metabolism, Habenula/metabolism, Loss of Function Mutation, Low Density Lipoprotein Receptor-Related Protein-6/metabolism, Membrane Proteins/metabolism, Neurogenesis, Neurons/metabolism, Receptors, Wnt/metabolism, Wnt Signaling Pathway, Zebrafish/embryology, Zebrafish Proteins/metabolism, Calcium Channels/genetics",

author = "Powell, {Gareth T} and Ana Faro and Yuguang Zhao and Heather Stickney and Laura Novellasdemunt and Pedro Henriques and Gaia Gestri and {Redhouse White}, Esther and Jingshan Ren and Weixian Lu and Young, {Rodrigo M} and Hawkins, {Thomas A} and Florencia Cavodeassi and Quenten Schwarz and Elena Dreosti and Raible, {David W} and Li, {Vivian S W} and Wright, {Gavin J} and Jones, {E Yvonne} and Wilson, {Stephen W}",

year = "2024",

month = may,

day = "3",

doi = "10.1126/science.ade6970",

language = "English",

volume = "384",

pages = "573--579",

journal = "Science (New York, N.Y.)",

issn = "0036-8075",

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Powell, GT, Faro, A, Zhao, Y, Stickney, H, Novellasdemunt, L, Henriques, P, Gestri, G, Redhouse White, E, Ren, J, Lu, W, Young, RM, Hawkins, TA, Cavodeassi, F, Schwarz, Q, Dreosti, E, Raible, DW, Li, VSW, Wright, GJ, Jones, EY & Wilson, SW 2024, 'Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain', Science (New York, N.Y.), vol. 384, no. 6695, pp. 573-579. https://doi.org/10.1126/science.ade6970

TY - JOUR

T1 - Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain

AU - Powell, Gareth T

AU - Faro, Ana

AU - Zhao, Yuguang

AU - Stickney, Heather

AU - Novellasdemunt, Laura

AU - Henriques, Pedro

AU - Gestri, Gaia

AU - Redhouse White, Esther

AU - Ren, Jingshan

AU - Lu, Weixian

AU - Young, Rodrigo M

AU - Hawkins, Thomas A

AU - Cavodeassi, Florencia

AU - Schwarz, Quenten

AU - Dreosti, Elena

AU - Raible, David W

AU - Li, Vivian S W

AU - Wright, Gavin J

AU - Jones, E Yvonne

AU - Wilson, Stephen W

PY - 2024/5/3

Y1 - 2024/5/3

N2 - 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.

AB - 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.

KW - Animals

KW - Frizzled Receptors/metabolism

KW - Habenula/metabolism

KW - Loss of Function Mutation

KW - Low Density Lipoprotein Receptor-Related Protein-6/metabolism

KW - Membrane Proteins/metabolism

KW - Neurogenesis

KW - Neurons/metabolism

KW - Receptors, Wnt/metabolism

KW - Wnt Signaling Pathway

KW - Zebrafish/embryology

KW - Zebrafish Proteins/metabolism

KW - Calcium Channels/genetics

U2 - 10.1126/science.ade6970

DO - 10.1126/science.ade6970

M3 - Article

C2 - 38696577

SN - 0036-8075

VL - 384

SP - 573

EP - 579

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6695

ER -