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

Autor: Powell GT; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK., Faro A; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK., Zhao Y; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Stickney H; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.; Departments of Otolaryngology-HNS and Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.; Ambry Genetics, Aliso Viejo, CA 92656, USA., Novellasdemunt L; The Francis Crick Institute, London, NW1 1AT, UK.; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain., Henriques P; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK., Gestri G; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK., Redhouse White E; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK., Ren J; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Lu W; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Young RM; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.; Institute of Ophthalmology, University College London, London EC1V 9EL, UK.; Center for Integrative Biology, Facultad de Ciencias, Universidad Mayor, Camino La Piramide 5750, 8580745 Santiago, Chile., Hawkins TA; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK., Cavodeassi F; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.; St. George's, University of London, London SW17 0RE, UK., Schwarz Q; Institute of Ophthalmology, University College London, London EC1V 9EL, UK., Dreosti E; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK., Raible DW; Departments of Otolaryngology-HNS and Biological Structure, University of Washington, Seattle, WA 98195-7420, USA., Li VSW; The Francis Crick Institute, London, NW1 1AT, UK., Wright GJ; Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.; Department of Biology, Hull York Medical School, York Biomedical Research Institute, University of York, York YO10 5DD, UK., Jones EY; Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK., Wilson SW; Cell and Developmental Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 May 03; Vol. 384 (6695), pp. 573-579. Date of Electronic Publication: 2024 May 02.
DOI: 10.1126/science.ade6970
Abstrakt: 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.
Databáze: MEDLINE
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