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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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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. |
format | Online Article Text |
id | pubmed-6727772 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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