Cachd1 is a novel Frizzled- and LRP6-interacting protein required for neurons to acquire left-right asymmetric character
Year: 2022
Type: preprint
Abstract: Neurons on left and right sides of the nervous system frequently show asymmetric properties but how these differences arise is poorly understood. Through a forward genetic screen in zebrafish, we find that loss of function of the transmembrane protein Cachd1 results in right-sided habenula neurons adopting left-sided character. Cachd1 is expressed in habenula neuron progenitors, functions symmetrically downstream of asymmetric environmental signals that determine laterality and influences timing of the normally left-right asymmetric patterns of neurogenesis. Unbiased screening for Cachd1 partners identified the Wnt co-receptor Frizzled7 and further biochemical and structural analysis revealed Cachd1 can bind simultaneously to Fzd proteins and Lrp6, bridging between these two Wnt co-receptors. Consistent with these structural studies, lrp6 mutant zebrafish show symmetric habenulae with left-sided character and epistasis experiments with other Wnt pathway genes support an in vivo role for Cachd1 in modulating Wnt pathway activity in the brain. Together, these studies identify Cachd1 as a conserved novel Wnt-receptor interacting protein with roles in regulating neurogenesis and neuronal identity.
Authors: 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
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: How is brain asymmetry established and what is it good for?., G1711412720, A forward genetic approach to identifying critical regulators of Wnt/Beta-catenin/Tcf signalling during brain and eye development., G2747125393, G2810127755, G3682808212, Pass the Wnt, from secretion to signalling, G4044271730, G4162283825, G4592998, Improved control of endemic foot-and-mouth disease by development of virus like particle vaccines, G5155016511, A forward genetic approach to identifying critical regulators of Wnt/Beta- catenin/Tcf signalling during brain and eye development., Resolving the basis of phenotypically variable hereditary abnormalities of eye formation, Improved control of endemic foot-and-mouth disease by development of virus like particle vaccines, How is brain asymmetry established and what is it good for?., The Structural Basis of Molecular Mechanisms in Cell Guidance and Adhesion., Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers., Morphogenesis and growth of the eye in health and disease, G8028381859, Pass the Wnt, from secretion to signalling, G8750956863
OpenAlex ID: W4280609297