Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/106561 https://doi.org/10.1371/journal.pbio.3000470 |
Resumo: | 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. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canalIn 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.Public Library of Science2020-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/106561http://hdl.handle.net/10316/106561https://doi.org/10.1371/journal.pbio.3000470eng1545-7885321505341545-7885Tait, Christine M.Chinnaiya, KavithaManning, ElizabethMurtaza, MariyamAshton, John-PaulFurley, NicholasHill, Chris J.Alves, C. HenriqueWijnholds, JanErdmann, Kai S.Furley, AndrewRashbass, PennyDas, Raman M.Storey, Kate G.Placzek, Marysiainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-04-11T08:20:07Zoai:estudogeral.uc.pt:10316/106561Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:22:59.940418Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal Tait, Christine M. |
title_short |
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_sort |
Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal |
author |
Tait, Christine M. |
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_role |
author |
author2 |
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 |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
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 |
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 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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-03 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/106561 http://hdl.handle.net/10316/106561 https://doi.org/10.1371/journal.pbio.3000470 |
url |
http://hdl.handle.net/10316/106561 https://doi.org/10.1371/journal.pbio.3000470 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1545-7885 32150534 1545-7885 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134118002294784 |