title: Myogenin (Myf4) upregulation in trans-differentiating fibroblasts from a congenital myopathy with arrest of myogenesis and defects of myotube formation.
abstract: Congenital myopathies often have an unclear aetiology. Here, we studied a novel case of a severe congenital myopathy with a failure of myotube formation. Polymerase chain reaction-based analysis was performed to characterize the expression patterns of the Desmin, p21, p57, and muscle regulatory factors (MRFs) MyoD, Myf4, Myf5 and Myf6 in differentiating skeletal muscle cells (SkMCs), normal human fibroblasts and patient-derived fibroblasts during trans-differentiation. The temporal and spatial pattern of MRFs was further characterized by immunocyto- and immunohistochemical stainings. In differentiating SkMCs, each MRF showed a characteristic expression pattern. Normal trans-differentiating fibroblasts formed myotubes and expressed all of the MRFs, which were detected. Interestingly, the patient's fibroblasts also showed some fusion events during trans-differentiation with a comparable expression profile for the MRFs, particularly, with increased expression of Myf4 and p21. Immunohistochemical analysis of normal and patient-derived skeletal musculature revealed that Myf4, which is downregulated during normal fetal development, was still present in patient-derived skeletal head muscle, which was also positive for Desmin and sarcomeric actin. The abnormal upregulation of Myf4 and p21 in the patient who suffered from a severe congenital myopathy suggests that the regulation of Myf4 and p21 gene expression during myogenesis might be of interest for further studies.
authors.affiliation: Department of Molecular Embryology, Institute of Anatomy and Cell Biology, Albert-Ludwigs-University Freiburg, Albertstrasse 17, 79104, Freiburg, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Weise
authors.forename: Fangping
authors.initials: F
authors.lastname: Dai
authors.forename: Felicitas
authors.initials: F
authors.lastname: Pröls
authors.forename: Uwe-Peter
authors.initials: UP
authors.lastname: Ketelsen
authors.forename: Ulrike
authors.initials: U
authors.lastname: Dohrmann
authors.forename: Mathias
authors.initials: M
authors.lastname: Kirsch
authors.forename: Beate
authors.initials: B
authors.lastname: Brand-Saberi
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002877:Chromosomes, Human; D020732:Cytogenetic Analysis; D017809:Fatal Outcome; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007231:Infant, Newborn; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D009132:Muscles / Q000002:abnormalities / Q000166:cytology / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*; D020914:Myopathies, Structural, Congenital / Q000378:metabolism*; D011110:Polymorphism, Genetic; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C503799:MYOG protein, human; D018008:Myogenin; D016283:Proto-Oncogene Proteins p21(ras)