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Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting

Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell–cell junctions, forming patent structures that support blood flow. Although s...

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Autores principales: Yoon, Christine, Choi, Colin, Stapleton, Sarah, Mirabella, Teodelinda, Howes, Caroline, Dong, Li, King, Jessica, Yang, Jinling, Oberai, Assad, Eyckmans, Jeroen, Chen, Christopher S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727772/
https://www.ncbi.nlm.nih.gov/pubmed/31318321
http://dx.doi.org/10.1091/mbc.E19-02-0076
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author Yoon, Christine
Choi, Colin
Stapleton, Sarah
Mirabella, Teodelinda
Howes, Caroline
Dong, Li
King, Jessica
Yang, Jinling
Oberai, Assad
Eyckmans, Jeroen
Chen, Christopher S.
author_facet Yoon, Christine
Choi, Colin
Stapleton, Sarah
Mirabella, Teodelinda
Howes, Caroline
Dong, Li
King, Jessica
Yang, Jinling
Oberai, Assad
Eyckmans, Jeroen
Chen, Christopher S.
author_sort Yoon, Christine
collection PubMed
description Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell–cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell–cell dissociation primarily between tip and stalk cells. Closer examination of cell–cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell–cell adhesions during collective motility.
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spelling pubmed-67277722019-10-07 Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting Yoon, Christine Choi, Colin Stapleton, Sarah Mirabella, Teodelinda Howes, Caroline Dong, Li King, Jessica Yang, Jinling Oberai, Assad Eyckmans, Jeroen Chen, Christopher S. Mol Biol Cell Articles Angiogenic sprouting is a critical process involved in vascular network formation within tissues. During sprouting, tip cells and ensuing stalk cells migrate collectively into the extracellular matrix while preserving cell–cell junctions, forming patent structures that support blood flow. Although several signaling pathways have been identified as controlling sprouting, it remains unclear to what extent this process is mechanoregulated. To address this question, we investigated the role of cellular contractility in sprout morphogenesis, using a biomimetic model of angiogenesis. Three-dimensional maps of mechanical deformations generated by sprouts revealed that mainly leader cells, not stalk cells, exert contractile forces on the surrounding matrix. Surprisingly, inhibiting cellular contractility with blebbistatin did not affect the extent of cellular invasion but resulted in cell–cell dissociation primarily between tip and stalk cells. Closer examination of cell–cell junctions revealed that blebbistatin impaired adherens-junction organization, particularly between tip and stalk cells. Using CRISPR/Cas9-mediated gene editing, we further identified NMIIA as the major isoform responsible for regulating multicellularity and cell contractility during sprouting. Together, these studies reveal a critical role for NMIIA-mediated contractile forces in maintaining multicellularity during sprouting and highlight the central role of forces in regulating cell–cell adhesions during collective motility. The American Society for Cell Biology 2019-07-22 /pmc/articles/PMC6727772/ /pubmed/31318321 http://dx.doi.org/10.1091/mbc.E19-02-0076 Text en © 2019 Yoon, Choi, Stapleton, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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.
spellingShingle Articles
Yoon, Christine
Choi, Colin
Stapleton, Sarah
Mirabella, Teodelinda
Howes, Caroline
Dong, Li
King, Jessica
Yang, Jinling
Oberai, Assad
Eyckmans, Jeroen
Chen, Christopher S.
Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting
title Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting
title_full Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting
title_fullStr Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting
title_full_unstemmed Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting
title_short Myosin IIA–mediated forces regulate multicellular integrity during vascular sprouting
title_sort myosin iia–mediated forces regulate multicellular integrity during vascular sprouting
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727772/
https://www.ncbi.nlm.nih.gov/pubmed/31318321
http://dx.doi.org/10.1091/mbc.E19-02-0076
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