Cachd1 interacts with Wnt receptors and regulates neuronal asymmetry in the zebrafish brain-Reference-Cited by-同舟云学术

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

Published:2024-05-03 Issue:6695 Volume:384 Page:573-579
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Powell Gareth T.¹²^ORCID,Faro Ana¹^ORCID,Zhao Yuguang³^ORCID,Stickney Heather¹⁴⁵^ORCID,Novellasdemunt Laura⁶⁷^ORCID,Henriques Pedro¹^ORCID,Gestri Gaia¹,Redhouse White Esther¹,Ren Jingshan³^ORCID,Lu Weixian³^ORCID,Young Rodrigo M.¹⁸⁹^ORCID,Hawkins Thomas A.¹^ORCID,Cavodeassi Florencia¹¹⁰^ORCID,Schwarz Quenten⁸^ORCID,Dreosti Elena¹^ORCID,Raible David W.⁴^ORCID,Li Vivian S. W.⁶^ORCID,Wright Gavin J.²¹¹^ORCID,Jones E. Yvonne³^ORCID,Wilson Stephen W.¹^ORCID

Affiliation:

1. Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.

2. Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.

3. Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

4. Departments of Otolaryngology-HNS and Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.

5. Ambry Genetics, Aliso Viejo, CA 92656, USA.

6. The Francis Crick Institute, London, NW1 1AT, UK.

7. Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.

8. Institute of Ophthalmology, University College London, London EC1V 9EL, UK.

9. Center for Integrative Biology, Facultad de Ciencias, Universidad Mayor, Camino La Piramide 5750, 8580745 Santiago, Chile.

10. St. George’s, University of London, London SW17 0RE, UK.

11. Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, York YO10 5DD, UK.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.ade6970

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