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- Catherine A. Risebro
- Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH,UK.
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- Richelle G. Searles
- Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH,UK.
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- Athalie A. D. Melville
- Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH,UK.
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- Elisabeth Ehler
- The Randall Centre of Cell and Molecular Biophysics and The Cardiovascular Division, King's College, London SE1 1UL, UK.
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- Nipurna Jina
- Molecular Haematology and Cancer Biology Unit, UCL Institute of Child Health,London WC1N 1EH, UK.
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- Sonia Shah
- Bloomsbury Centre for Bioinformatics, Department of Computer Science,University College London, Gower Street, London WC1E 6BT, UK.
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- Jacky Pallas
- Bloomsbury Centre for Bioinformatics, Department of Computer Science,University College London, Gower Street, London WC1E 6BT, UK.
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- Mike Hubank
- Molecular Haematology and Cancer Biology Unit, UCL Institute of Child Health,London WC1N 1EH, UK.
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- Miriam Dillard
- Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
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- Natasha L. Harvey
- Division of Haematology, The Hanson Institute, Adelaide, South Australia 5000,Australia.
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- Robert J. Schwartz
- Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
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- Kenneth R. Chien
- Massachusetts General Hospital Cardiovascular Research Center, Boston, MA 02114, USA.
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- Guillermo Oliver
- Department of Genetics and Tumor Cell Biology, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
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- Paul R. Riley
- Molecular Medicine Unit, UCL Institute of Child Health, London WC1N 1EH,UK.
説明
<jats:p>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 α-actinin, N-RAP and zyxin, which collectively function to maintain an actin-α-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.</jats:p>
収録刊行物
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- Development
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Development 136 (3), 495-505, 2009-02-01
The Company of Biologists
