Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal
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 mi...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108746/ https://www.ncbi.nlm.nih.gov/pubmed/32150534 http://dx.doi.org/10.1371/journal.pbio.3000470 |
_version_ | 1783512838007947264 |
---|---|
author | 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 |
author_facet | 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 |
author_sort | Tait, Christine M. |
collection | PubMed |
description | 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 Crb2(F/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. |
format | Online Article Text |
id | pubmed-7108746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71087462020-04-03 Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal 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 PLoS Biol Research Article 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 Crb2(F/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. Public Library of Science 2020-03-09 /pmc/articles/PMC7108746/ /pubmed/32150534 http://dx.doi.org/10.1371/journal.pbio.3000470 Text en © 2020 Tait et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article 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 Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
title | Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
title_full | Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
title_fullStr | Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
title_full_unstemmed | Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
title_short | Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
title_sort | crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108746/ https://www.ncbi.nlm.nih.gov/pubmed/32150534 http://dx.doi.org/10.1371/journal.pbio.3000470 |
work_keys_str_mv | AT taitchristinem crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT chinnaiyakavitha crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT manningelizabeth crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT murtazamariyam crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT ashtonjohnpaul crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT furleynicholas crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT hillchrisj crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT alveschenrique crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT wijnholdsjan crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT erdmannkais crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT furleyandrew crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT rashbasspenny crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT dasramanm crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT storeykateg crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal AT placzekmarysia crumbs2mediatesventricularlayerremodellingtoformthespinalcordcentralcanal |