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N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube

Neural progenitors are organized as a pseudostratified epithelium held together by adherens junctions (AJs), multiprotein complexes composed of cadherins and α- and β-catenin. Catenins are known to control neural progenitor division; however, it is not known whether they function in this capacity as...

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Detalles Bibliográficos
Autores principales: Chalasani, Kavita, Brewster, Rachel M.
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084673/
https://www.ncbi.nlm.nih.gov/pubmed/21389116
http://dx.doi.org/10.1091/mbc.E10-08-0675
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author Chalasani, Kavita
Brewster, Rachel M.
author_facet Chalasani, Kavita
Brewster, Rachel M.
author_sort Chalasani, Kavita
collection PubMed
description Neural progenitors are organized as a pseudostratified epithelium held together by adherens junctions (AJs), multiprotein complexes composed of cadherins and α- and β-catenin. Catenins are known to control neural progenitor division; however, it is not known whether they function in this capacity as cadherin binding partners, as there is little evidence that cadherins themselves regulate neural proliferation. We show here that zebrafish N-cadherin (N-cad) restricts cell proliferation in the dorsal region of the neural tube by regulating cell-cycle length. We further reveal that N-cad couples cell-cycle exit and differentiation, as a fraction of neurons are mitotic in N-cad mutants. Enhanced proliferation in N-cad mutants is mediated by ligand-independent activation of Hedgehog (Hh) signaling, possibly caused by defective ciliogenesis. Furthermore, depletion of Hh signaling results in the loss of junctional markers. We therefore propose that N-cad restricts the response of dorsal neural progenitors to Hh and that Hh signaling limits the range of its own activity by promoting AJ assembly. Taken together, these observations emphasize a key role for N-cad–mediated adhesion in controlling neural progenitor proliferation. In addition, these findings are the first to demonstrate a requirement for cadherins in synchronizing cell-cycle exit and differentiation and a reciprocal interaction between AJs and Hh signaling.
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spelling pubmed-30846732011-07-16 N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube Chalasani, Kavita Brewster, Rachel M. Mol Biol Cell Articles Neural progenitors are organized as a pseudostratified epithelium held together by adherens junctions (AJs), multiprotein complexes composed of cadherins and α- and β-catenin. Catenins are known to control neural progenitor division; however, it is not known whether they function in this capacity as cadherin binding partners, as there is little evidence that cadherins themselves regulate neural proliferation. We show here that zebrafish N-cadherin (N-cad) restricts cell proliferation in the dorsal region of the neural tube by regulating cell-cycle length. We further reveal that N-cad couples cell-cycle exit and differentiation, as a fraction of neurons are mitotic in N-cad mutants. Enhanced proliferation in N-cad mutants is mediated by ligand-independent activation of Hedgehog (Hh) signaling, possibly caused by defective ciliogenesis. Furthermore, depletion of Hh signaling results in the loss of junctional markers. We therefore propose that N-cad restricts the response of dorsal neural progenitors to Hh and that Hh signaling limits the range of its own activity by promoting AJ assembly. Taken together, these observations emphasize a key role for N-cad–mediated adhesion in controlling neural progenitor proliferation. In addition, these findings are the first to demonstrate a requirement for cadherins in synchronizing cell-cycle exit and differentiation and a reciprocal interaction between AJs and Hh signaling. The American Society for Cell Biology 2011-05-01 /pmc/articles/PMC3084673/ /pubmed/21389116 http://dx.doi.org/10.1091/mbc.E10-08-0675 Text en © 2011 Chalasani and Brewster. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,“ “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Chalasani, Kavita
Brewster, Rachel M.
N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
title N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
title_full N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
title_fullStr N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
title_full_unstemmed N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
title_short N-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
title_sort n-cadherin–mediated cell adhesion restricts cell proliferation in the dorsal neural tube
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084673/
https://www.ncbi.nlm.nih.gov/pubmed/21389116
http://dx.doi.org/10.1091/mbc.E10-08-0675
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