The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation
Autor: | Ida Salmela, Riikka Kivelä, Kari Alitalo, Tatiana V. Petrova, Zoltán Wiener, Yen Hoang Nguyen, Heikki A. Koistinen |
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Přispěvatelé: | Research Programs Unit, Translational Cancer Biology (TCB) Research Programme, Clinicum, Department of Medicine, Endokrinologian yksikkö, Kari Alitalo / Principal Investigator, Kivelä Lab |
Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine PROMOTES Cellular differentiation Muscle Fibers Skeletal General Physics and Astronomy CALCINEURIN ACTIVATION Mice Myocyte Receptor Notch1 Cells Cultured GENE-EXPRESSION Multidisciplinary Cell Differentiation NFAT Hedgehog signaling pathway Cell biology Crosstalk (biology) NOTCH medicine.anatomical_structure SKELETAL-MUSCLE Female Stem cell STEM-CELLS Signal Transduction Satellite Cells Skeletal Muscle Science Mice Transgenic Biology Article General Biochemistry Genetics and Molecular Biology SIGNALING PATHWAYS 03 medical and health sciences REGENERATION medicine Animals Humans Transcription factor Homeodomain Proteins NFATC Transcription Factors Tumor Suppressor Proteins Skeletal muscle General Chemistry Mice Inbred C57BL 030104 developmental biology SLOW Gene Expression Regulation 3111 Biomedicine |
Zdroj: | Nature Communications, vol. 7, pp. 13124 Nature Communications Nature Communications, Vol 7, Iss 1, Pp 1-11 (2016) |
Popis: | The remarkable adaptive and regenerative capacity of skeletal muscle is regulated by several transcription factors and pathways. Here we show that the transcription factor Prox1 is an important regulator of myoblast differentiation and of slow muscle fibre type. In both rodent and human skeletal muscles Prox1 is specifically expressed in slow muscle fibres and in muscle stem cells called satellite cells. Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of the gene program of slow muscle fibre type. Using lineage-tracing we show that Prox1-positive satellite cells differentiate into muscle fibres. Furthermore, we provide evidence that Prox1 is a critical transcription factor for the differentiation of myoblasts via bi-directional crosstalk with Notch1. These results identify Prox1 as an essential transcription factor that regulates skeletal muscle phenotype and myoblast differentiation by interacting with the NFAT and Notch pathways. Skeletal muscle has remarkable adaptive and regenerative capacity. Here the authors show that the transcription factor Prox1 is necessary for maintenance of slow muscle fibre types via activation of NFAT signalling, and for myoblast differentiation via cross-talk with the Notch signalling pathway. |
Databáze: | OpenAIRE |
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