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Title: | Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal | Authors: | Tait, Christine M. Chinnaiya, Kavitha Manning, Elizabeth Murtaza, Mariyam Ashton, John-Paul Furley, Nicholas Hill, Chris J. Alves, C. Henrique Wijnholds, Jan Erdmann, Kai S. Furley, Andrew Rashbass, Penny Das, Raman M. Storey, Kate G. Placzek, Marysia |
Issue Date: | Mar-2020 | Publisher: | Public Library of Science | Project: | This research has been supported by grants fromthe UK Medical Research Council (https://mrc.ukri.org/; G0401310 to MP, the Wellcome Trust (https://wellcome.ac.uk/; 212247Z18Z to MP; 102817A1A to KGS; 208401 to KGS) and The European Union (https://ec. europa.eu/research/fp7/index_en.cfm; HEALTH F2- 2008-200234 to PR and JW and The Netherlands Organisation for Health Research and Development (https://www.zonmw.nl/en/; ZonMw 43200004 to JW) | Serial title, monograph or event: | PLoS Biology | Volume: | 18 | Issue: | 3 | Abstract: | 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. | URI: | https://hdl.handle.net/10316/106561 | ISSN: | 1545-7885 | DOI: | 10.1371/journal.pbio.3000470 | Rights: | openAccess |
Appears in Collections: | I&D ICBR - Artigos em Revistas Internacionais |
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