Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy.
Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-rel...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2014
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| _version_ | 1797060304023060480 |
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| author | Petchey, L Risebro, C Vieira, J Roberts, T Bryson, J Greensmith, L Lythgoe, M Riley, P |
| author_facet | Petchey, L Risebro, C Vieira, J Roberts, T Bryson, J Greensmith, L Lythgoe, M Riley, P |
| author_sort | Petchey, L |
| collection | OXFORD |
| description | Correct regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease. |
| first_indexed | 2024-03-06T20:15:15Z |
| format | Journal article |
| id | oxford-uuid:2bee744d-188e-44de-a22c-b1acd553f2cd |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:15:15Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:2bee744d-188e-44de-a22c-b1acd553f2cd2022-03-26T12:33:53ZLoss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2bee744d-188e-44de-a22c-b1acd553f2cdEnglishSymplectic Elements at OxfordNational Academy of Sciences2014Petchey, LRisebro, CVieira, JRoberts, TBryson, JGreensmith, LLythgoe, MRiley, PCorrect regulation of troponin and myosin contractile protein gene isoforms is a critical determinant of cardiac and skeletal striated muscle development and function, with misexpression frequently associated with impaired contractility or disease. Here we reveal a novel requirement for Prospero-related homeobox factor 1 (Prox1) during mouse heart development in the direct transcriptional repression of the fast-twitch skeletal muscle genes troponin T3, troponin I2, and myosin light chain 1. A proportion of cardiac-specific Prox1 knockout mice survive beyond birth with hearts characterized by marked overexpression of fast-twitch genes and postnatal development of a fatal dilated cardiomyopathy. Through conditional knockout of Prox1 from skeletal muscle, we demonstrate a conserved requirement for Prox1 in the repression of troponin T3, troponin I2, and myosin light chain 1 between cardiac and slow-twitch skeletal muscle and establish Prox1 ablation as sufficient to cause a switch from a slow- to fast-twitch muscle phenotype. Our study identifies conserved roles for Prox1 between cardiac and skeletal muscle, specifically implicated in slow-twitch fiber-type specification, function, and cardiomyopathic disease. |
| spellingShingle | Petchey, L Risebro, C Vieira, J Roberts, T Bryson, J Greensmith, L Lythgoe, M Riley, P Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. |
| title | Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. |
| title_full | Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. |
| title_fullStr | Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. |
| title_full_unstemmed | Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. |
| title_short | Loss of Prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy. |
| title_sort | loss of prox1 in striated muscle causes slow to fast skeletal muscle fiber conversion and dilated cardiomyopathy |
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