Prox1 maintains muscle structure and growth in the developing heart.
Impaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross my...
Main Authors: | , , , , , , , , , , , , , |
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Format: | Journal article |
Language: | English |
Published: |
2009
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author | Risebro, C Searles, R Melville, A Ehler, E Jina, N Shah, S Pallas, J Hubank, M Dillard, M Harvey, N Schwartz, R Chien, K Oliver, G Riley, P |
author_facet | Risebro, C Searles, R Melville, A Ehler, E Jina, N Shah, S Pallas, J Hubank, M Dillard, M Harvey, N Schwartz, R Chien, K Oliver, G Riley, P |
author_sort | Risebro, C |
collection | OXFORD |
description | Impaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross myofibril disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is required for direct transcriptional regulation of the genes encoding the structural proteins alpha-actinin, N-RAP and zyxin, which collectively function to maintain an actin-alpha-actinin interaction as the fundamental association of the sarcomere. Aspects of abnormal heart development and the manifestation of a subset of muscular-based disease have previously been attributed to mutations in key structural proteins. Our study reveals an essential requirement for direct transcriptional regulation of sarcomere integrity, in the context of enabling foetal cardiomyocyte hypertrophy, maintenance of contractile function and progression towards inherited or acquired myopathic disease. |
first_indexed | 2024-03-06T23:04:03Z |
format | Journal article |
id | oxford-uuid:632e934c-96ca-49af-addb-c1da3f14dd96 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-06T23:04:03Z |
publishDate | 2009 |
record_format | dspace |
spelling | oxford-uuid:632e934c-96ca-49af-addb-c1da3f14dd962022-03-26T18:11:07ZProx1 maintains muscle structure and growth in the developing heart.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:632e934c-96ca-49af-addb-c1da3f14dd96EnglishSymplectic Elements at Oxford2009Risebro, CSearles, RMelville, AEhler, EJina, NShah, SPallas, JHubank, MDillard, MHarvey, NSchwartz, RChien, KOliver, GRiley, PImpaired cardiac muscle growth and aberrant myocyte arrangement underlie congenital heart disease and cardiomyopathy. We show that cardiac-specific inactivation of the murine homeobox transcription factor Prox1 results in the disruption of expression and localisation of sarcomeric proteins, gross myofibril disarray and growth-retarded hearts. Furthermore, we demonstrate that Prox1 is required for direct transcriptional regulation of the genes encoding the structural proteins alpha-actinin, N-RAP and zyxin, which collectively function to maintain an actin-alpha-actinin interaction as the fundamental association of the sarcomere. Aspects of abnormal heart development and the manifestation of a subset of muscular-based disease have previously been attributed to mutations in key structural proteins. Our study reveals an essential requirement for direct transcriptional regulation of sarcomere integrity, in the context of enabling foetal cardiomyocyte hypertrophy, maintenance of contractile function and progression towards inherited or acquired myopathic disease. |
spellingShingle | Risebro, C Searles, R Melville, A Ehler, E Jina, N Shah, S Pallas, J Hubank, M Dillard, M Harvey, N Schwartz, R Chien, K Oliver, G Riley, P Prox1 maintains muscle structure and growth in the developing heart. |
title | Prox1 maintains muscle structure and growth in the developing heart. |
title_full | Prox1 maintains muscle structure and growth in the developing heart. |
title_fullStr | Prox1 maintains muscle structure and growth in the developing heart. |
title_full_unstemmed | Prox1 maintains muscle structure and growth in the developing heart. |
title_short | Prox1 maintains muscle structure and growth in the developing heart. |
title_sort | prox1 maintains muscle structure and growth in the developing heart |
work_keys_str_mv | AT risebroc prox1maintainsmusclestructureandgrowthinthedevelopingheart AT searlesr prox1maintainsmusclestructureandgrowthinthedevelopingheart AT melvillea prox1maintainsmusclestructureandgrowthinthedevelopingheart AT ehlere prox1maintainsmusclestructureandgrowthinthedevelopingheart AT jinan prox1maintainsmusclestructureandgrowthinthedevelopingheart AT shahs prox1maintainsmusclestructureandgrowthinthedevelopingheart AT pallasj prox1maintainsmusclestructureandgrowthinthedevelopingheart AT hubankm prox1maintainsmusclestructureandgrowthinthedevelopingheart AT dillardm prox1maintainsmusclestructureandgrowthinthedevelopingheart AT harveyn prox1maintainsmusclestructureandgrowthinthedevelopingheart AT schwartzr prox1maintainsmusclestructureandgrowthinthedevelopingheart AT chienk prox1maintainsmusclestructureandgrowthinthedevelopingheart AT oliverg prox1maintainsmusclestructureandgrowthinthedevelopingheart AT rileyp prox1maintainsmusclestructureandgrowthinthedevelopingheart |