title: The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation.
abstract: 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.
authors.affiliation: Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.|Translational Cancer Biology Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, Helsinki 00014, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Kivelä
authors.affiliation: Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.|Translational Cancer Biology Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, Helsinki 00014, Finland.
authors.forename: Ida
authors.initials: I
authors.lastname: Salmela
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2U, Tukholmankatu 8, Helsinki 00290, Finland.|Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 340, Helsinki 00029, Finland.
authors.forename: Yen Hoang
authors.initials: YH
authors.lastname: Nguyen
authors.affiliation: Department of Fundamental Oncology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne (UNIL), and Division of Experimental Pathology, Institute of Pathology, CHUV, CH-1066 Epalinges, Switzerland.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Petrova
authors.affiliation: Minerva Foundation Institute for Medical Research, Biomedicum Helsinki 2U, Tukholmankatu 8, Helsinki 00290, Finland.|Department of Medicine and Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 340, Helsinki 00029, Finland.
authors.forename: Heikki A
authors.identifier: 0000-0001-7870-070X
authors.initials: HA
authors.lastname: Koistinen
authors.affiliation: Translational Cancer Biology Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, Helsinki 00014, Finland.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Wiener
authors.affiliation: Wihuri Research Institute, Biomedicum Helsinki, Haartmaninkatu 8, Helsinki 00290, Finland.|Translational Cancer Biology Program, Faculty of Medicine, University of Helsinki, P.O. Box 63, Helsinki 00014, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism / Q000502:physiology*; D032496:Satellite Cells, Skeletal Muscle / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D018398:Homeodomain Proteins; D050778:NFATC Transcription Factors; D051881:Receptor, Notch1; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein