title: Noggin inactivation affects the number and differentiation potential of muscle progenitor cells in vivo.
abstract: Inactivation of Noggin, a secreted antagonist of Bone Morphogenetic Proteins (BMPs), in mice leads, among others, to severe malformations of the appendicular skeleton and defective skeletal muscle fibers. To determine the molecular basis of the phenotype, we carried out a histomorphological and molecular analysis of developing muscles Noggin(-/-) mice. We show that in 18.5 dpc embryos there is a marked reduction in muscle fiber size and a failure of nuclei migration towards the cell membrane. Molecularly, the absence of Noggin results in an increased BMP signaling in muscle tissue as shown by the increase in SMAD1/5/8 phosphorylation, concomitant with the induction of BMP target genes such as Id1, 2, 3 as well as Msx1. Finally, upon removal of Noggin, the number of mesenchymal Pax7(+) muscle precursor cells is reduced and they are more prone to differentiate into adipocytes in vitro. Thus, our results highlight the importance of Noggin/BMP balance for myogenic commitment of early fetal progenitor cells.
authors: Translational Cardiomyology Lab, Stem Cell Biology and Embryology, Dept. Development and Regeneration, KU Leuven, Belgium.|Laboratory of Experimental Medicine and Clinical Pathology, Dept. Clinical and Biological Sciences, University of Turin, Italy.
authors: Domiziana
authors: D
authors: Costamagna
authors: Department of Development and Regeneration, Laboratory for Developmental and Stem Cell Biology, Skeletal Biology and Engineering Research Centre, KU Leuven, Belgium.
authors: Hendrik
authors: H
authors: Mommaerts
authors: Translational Cardiomyology Lab, Stem Cell Biology and Embryology, Dept. Development and Regeneration, KU Leuven, Belgium.|Division of Human Anatomy, Dept. of Public Health, Experimental and Forensic Medicine, University of Pavia, Italy.
authors: Maurilio
authors: M
authors: Sampaolesi
authors: Department of Development and Regeneration, Laboratory for Developmental and Stem Cell Biology, Skeletal Biology and Engineering Research Centre, KU Leuven, Belgium.|Department of Biochemistry and Molecular Biology, Medical University, Lublin, Poland.
authors: Przemko
authors: P
authors: Tylzanowski
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D000099176:Noggin Protein