Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal
| Autor: | Elizabeth M. Manning, John-Paul Ashton, C. Henrique Alves, Jan Wijnholds, Mariyam Murtaza, Marysia Placzek, Andrew J.W. Furley, Kai S. Erdmann, Christopher J. Hill, Raman M. Das, P. Rashbass, Kavitha Chinnaiya, Nicholas Furley, Kate G. Storey, Christine M. Tait |
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| Přispěvatelé: | Netherlands Institute for Neuroscience (NIN) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Embryology Cell Chick Embryo Nervous System Biochemistry Madin Darby Canine Kidney Cells Nestin 0302 clinical medicine Animal Cells Cell polarity Medicine and Health Sciences Biology (General) Mice Knockout General Neuroscience Stem Cells Gene Expression Regulation Developmental Cell Polarity Transmembrane protein Cell biology medicine.anatomical_structure Spinal Cord Embryogenesis Stem cell Anatomy Cellular Types General Agricultural and Biological Sciences Research Article Cell Physiology Imaging Techniques QH301-705.5 Mice Transgenic Biology Research and Analysis Methods Time-Lapse Imaging Green Fluorescent Protein General Biochemistry Genetics and Molecular Biology Tight Junctions 03 medical and health sciences Dogs Live cell imaging Fluorescence Imaging medicine Cell Adhesion Animals Humans Progenitor General Immunology and Microbiology SOXB1 Transcription Factors Embryos Membrane Proteins Biology and Life Sciences Proteins Cell Biology Spinal cord Mice Inbred C57BL Neuroanatomy Luminescent Proteins Cytoskeletal Proteins 030104 developmental biology HEK293 Cells 030217 neurology & neurosurgery Developmental Biology Neuroscience |
| Zdroj: | PLoS Biology, Vol 18, Iss 3, p e3000470 (2020) Tait, C M, Chinnaiya, K, Manning, E, Murtaza, M, Ashton, J-P, Furley, N, Hill, C J, Alves, C H, Wijnholds, J, Erdmann, K S, Furley, A, Rashbass, P, Das, R M, Storey, K G & Placzek, M 2020, ' Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal ', PLoS Biology, vol. 18, no. 3, pp. e3000470 . https://doi.org/10.1371/journal.pbio.3000470 PLoS Biology, 18(3). PUBLIC LIBRARY SCIENCE PLoS Biology, 18(3). Public Library of Science PLoS Biology |
| ISSN: | 1545-7885 1544-9173 |
| Popis: | In the spinal cord, the central canal forms through a poorly understood process termed dorsal collapse that involves attrition and remodelling of pseudostratified ventricular layer (VL) cells. Here, we use mouse and chick models to show that dorsal ventricular layer (dVL) cells adjacent to dorsal midline Nestin(+) radial glia (dmNes+RG) down-regulate apical polarity proteins, including Crumbs2 (CRB2) and delaminate in a stepwise manner; live imaging shows that as one cell delaminates, the next cell ratchets up, the dmNes+RG endfoot ratchets down, and the process repeats. We show that dmNes+RG secrete a factor that promotes loss of cell polarity and delamination. This activity is mimicked by a secreted variant of Crumbs2 (CRB2S) which is specifically expressed by dmNes+RG. In cultured MDCK cells, CRB2S associates with apical membranes and decreases cell cohesion. Analysis of Crb2F/F/Nestin-Cre+/− mice, and targeted reduction of Crb2/CRB2S in slice cultures reveal essential roles for transmembrane CRB2 (CRB2TM) and CRB2S on VL cells and dmNes+RG, respectively. We propose a model in which a CRB2S–CRB2TM interaction promotes the progressive attrition of the dVL without loss of overall VL integrity. This novel mechanism may operate more widely to promote orderly progenitor delamination. During prenatal development, the lumen of the vertebrate spinal cord is remodelled into the central canal when progenitor cells progressively delaminate. Imaging studies in the mouse provide novel insights into how roof plate–derived dorsal midline glia secrete a factor that regulates local delamination and ratcheting. Gain- and loss-of-function approaches show that the apical polarity protein, Crumbs2, mediates these events, and highlight the role of a secreted variant of Crumbs2. |
| Databáze: | OpenAIRE |
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