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Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development

Matrix Metalloproteinases (Mmps) degrade glycoproteins and proteoglycans of the extracellular matrix (ECM) or cell surface and are crucial for morphogenesis. Mmps and their inhibitors are expressed during early stages of cardiac development in vertebrates and expression is altered in multiple congen...

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Autores principales: Raza, Qanber S., Vanderploeg, Jessica L., Jacobs, J. Roger
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305246/
https://www.ncbi.nlm.nih.gov/pubmed/28192468
http://dx.doi.org/10.1371/journal.pone.0171905
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author Raza, Qanber S.
Vanderploeg, Jessica L.
Jacobs, J. Roger
author_facet Raza, Qanber S.
Vanderploeg, Jessica L.
Jacobs, J. Roger
author_sort Raza, Qanber S.
collection PubMed
description Matrix Metalloproteinases (Mmps) degrade glycoproteins and proteoglycans of the extracellular matrix (ECM) or cell surface and are crucial for morphogenesis. Mmps and their inhibitors are expressed during early stages of cardiac development in vertebrates and expression is altered in multiple congenital cardiomyopathies such as cardia bifida. Drosophila genome encodes two copies of Mmps, Mmp1 and Mmp2 whereas in humans up to 25 Mmps have been identified with overlapping functions. We investigated the role of Mmps during embryonic heart development in Drosophila, a process which is morphogenetically similar to early heart tube formation in vertebrates. We demonstrate that the two Mmps in Drosophila have distinct and overlapping roles in cell motility, cell adhesion and cardiac lumenogenesis. We determined that Mmp1 and Mmp2 promote Leading Edge membrane dynamics of cardioblasts during collective migration. Mmp2 is essential for cardiac lumen formation, and mutants generate a cardia bifida phenotype. Mmp1 is required for luminal expansion. Mmp1 and Mmp2 both localise to the basal domains of cardiac cells, however, occupy non-overlapping domains apically. Mmp1 and Mmp2 regulate the proteoglycan composition and size of the apical and basal ECM, yet only Mmp2 is required to restrict ECM assembly to the lumen. Mmp1 negatively regulates the size of the adhesive Cadherin cell surface domain, whereas in a complementary fashion, Mmp2 negatively regulates the size of the Integrin-ECM domain and thereby prescribes the domain to establish and restrict Slit morphogen signalling. Inhibition of Mmp activity through ectopic expression of Tissue Inhibitor of Metalloproteinase in the ectoderm blocks lumen formation. Therefore, Mmp expression and function identifies ECM differentiation and remodelling as a key element for cell polarisation and organogenesis.
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spelling pubmed-53052462017-02-28 Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development Raza, Qanber S. Vanderploeg, Jessica L. Jacobs, J. Roger PLoS One Research Article Matrix Metalloproteinases (Mmps) degrade glycoproteins and proteoglycans of the extracellular matrix (ECM) or cell surface and are crucial for morphogenesis. Mmps and their inhibitors are expressed during early stages of cardiac development in vertebrates and expression is altered in multiple congenital cardiomyopathies such as cardia bifida. Drosophila genome encodes two copies of Mmps, Mmp1 and Mmp2 whereas in humans up to 25 Mmps have been identified with overlapping functions. We investigated the role of Mmps during embryonic heart development in Drosophila, a process which is morphogenetically similar to early heart tube formation in vertebrates. We demonstrate that the two Mmps in Drosophila have distinct and overlapping roles in cell motility, cell adhesion and cardiac lumenogenesis. We determined that Mmp1 and Mmp2 promote Leading Edge membrane dynamics of cardioblasts during collective migration. Mmp2 is essential for cardiac lumen formation, and mutants generate a cardia bifida phenotype. Mmp1 is required for luminal expansion. Mmp1 and Mmp2 both localise to the basal domains of cardiac cells, however, occupy non-overlapping domains apically. Mmp1 and Mmp2 regulate the proteoglycan composition and size of the apical and basal ECM, yet only Mmp2 is required to restrict ECM assembly to the lumen. Mmp1 negatively regulates the size of the adhesive Cadherin cell surface domain, whereas in a complementary fashion, Mmp2 negatively regulates the size of the Integrin-ECM domain and thereby prescribes the domain to establish and restrict Slit morphogen signalling. Inhibition of Mmp activity through ectopic expression of Tissue Inhibitor of Metalloproteinase in the ectoderm blocks lumen formation. Therefore, Mmp expression and function identifies ECM differentiation and remodelling as a key element for cell polarisation and organogenesis. Public Library of Science 2017-02-13 /pmc/articles/PMC5305246/ /pubmed/28192468 http://dx.doi.org/10.1371/journal.pone.0171905 Text en © 2017 Raza 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
Raza, Qanber S.
Vanderploeg, Jessica L.
Jacobs, J. Roger
Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
title Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
title_full Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
title_fullStr Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
title_full_unstemmed Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
title_short Matrix Metalloproteinases are required for membrane motility and lumenogenesis during Drosophila heart development
title_sort matrix metalloproteinases are required for membrane motility and lumenogenesis during drosophila heart development
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305246/
https://www.ncbi.nlm.nih.gov/pubmed/28192468
http://dx.doi.org/10.1371/journal.pone.0171905
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