Top

Published in:

01-11-2006 | Original Article

Myogenin (Myf4) upregulation in trans-differentiating fibroblasts from a congenital myopathy with arrest of myogenesis and defects of myotube formation

Authors: Claudia Weise, Fangping Dai, Felicitas Pröls, Uwe-Peter Ketelsen, Ulrike Dohrmann, Mathias Kirsch, Beate Brand-Saberi

Published in: Brain Structure and Function | Issue 6/2006

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.

Kindly provided by the Institute of Pathology, University of Freiburg.

Andrés V, Walsh K (1996) Myogenin expression, cell cycle withdrawal, and phenotypic differentiation are temporally separable events that precede cell fusion upon myogenesis. J Cell Biol 132:657–666PubMedCrossRef

Arnold HH, Winter B (1998) Muscle differentiation: more complexity to the network of myogenic regulators. Curr Biol 8:539–544CrossRef

Bailey P, Holowacz T, Lassar AB (2001) The origin of skeletal muscle stem cells in the embryo and the adult. Curr Opin Cell Biol 13:679–689PubMedCrossRef

Bornemann A, Anderson LV (2000) Diagnostic protein expression in human muscle biopsies. Brain Pathol 10:193–214PubMedCrossRef

Bornemann A, Goebel HH (2001) Congenital myopathies. Brain Pathol 11:206–217PubMedCrossRef

Brand-Saberi B, Christ B (2000) Evolution and development of distinct cell lineages derived from somites. Curr Top Dev Biol 48:1–42PubMedCrossRef

Braun T, Arnold HH (1995) Inactivation of Myf-6 and Myf-5 genes in mice leads to alterations in skeletal muscle development. EMBO J 14:1176–1186PubMed

Braun T, Rudnicki MA, Arnold HH, Jaenisch R (1992) Targeted inactivation of the muscle regulatory gene Myf-5 results in abnormal rib development and perinatal death. Cell 71:369–382PubMedCrossRef

Espinos E, Liu JH, Bader CR, Bernheim L (2001) Efficient non-viral DNA-mediated gene transfer to human primary myoblasts using electroporation. Neuromuscul Disord 11:341–349PubMedCrossRef

Folpe AL (2002) MyoD1 and myogenin expression in human neoplasia: a review and update. Adv Anat Pathol 9:198–203PubMedCrossRef

Fougerousse F, Durand M, Lopez S, Suel L, Demignon J, Thornton C, Ozaki H, Kawakami K, Barbet P, Beckmann J, Maire P (2002) Six and Eya expression during human somitogenesis and MyoD gene family activation. J Muscle Res Cell Motil 23:255–264PubMedCrossRef

Hacker A, Guthrie S (1998) A distinct developmental programme for the cranial paraxial mesoderm in the chick embryo. Development 125:3461–3472PubMed

Hasty P, Bradley A, Morris JH, Edmondson DG, Venuti JM, Olson EN, Klein WH (1993) Muscle deficiency and neonatal death in mice with a targeted mutation in the myogenin gene. Nature 364:501–506PubMedCrossRef

Hawke TJ, Meeson AP, Jiang N, Graham S, Hutcheson K, DiMario JM, Garry DJ (2003) p21 is essential for normal myogenic progenitor cell function in regenerating skeletal muscle. Am J Physiol Cell Physiol 285:C1019—C1027PubMed

Kablar B, Krastel K, Tajbakhsh S, Rudnicki MA (2003) Myf5 and MyoD activation define independent myogenic compartments during embryonic development. Dev Biol 258:307–318PubMedCrossRef

Kadi F, Johansson F, Johansson R, Sjöström M, Henriksson J (2004) Effects of one bout of endurance exercise on the expression of myogenin in human quadriceps muscle. Histochem Cell Biol 121:329–334PubMedCrossRef

Kerst B, Mennerich D, Schuelke M, Stoltenburg-Didinger G, Moers A, Gossrau R, Landeghem FKH, Speer A, Braun T, Hübner C (2000) Heterozygous myogenic factor 6 mutation associated with myopathy and severe course of Becker muscular dystrophy. Neuromuscul Disord 10:572–577PubMedCrossRef

Ketelsen UP (1999) Congenital myopathy with arrest of myogenesis before fusion of myoblasts to myotubes. Nervenheilkunde 7a:13–14

Ketelsen UP, Brand-Saberi B, Uhlenberg B, Wagner M, Laberke HG, Omran H (2005) Congenital myopathy with arrest of myogenesis prior to formation of myotubes. Neuropaediatrics 36:246–251 CrossRef

Mootoosamy RC, Dietrich S (2002) Distinct regulatory cascades for head and trunk myogenesis. Development 129:573–583PubMed

Muntoni F, Brown S, Sewry C, Patel K (2002) Muscle development genes: their relevance in neuromuscular disorders. Neuromuscul Disord 12:438–446PubMedCrossRef

Nabeshima Y, Hanaoka K, Hayasaka M, Esumi E, Li S, Nonaka I, Nabeshima YI (1993) Myogenin gene disruption results in perinatal lethality because of severe muscle defect. Nature 364:532–535PubMedCrossRef

Olivé M, Martinez-Matos JA, Ferrer I (1997) Expression of myogenic regulatory factors (MRFs) in human neuromuscular disorders. Neuropathol Appl Neurobiol 23:475–482PubMedCrossRef

Parker MH, Seale P, Rudnicki MA (2003) Looking back to the embryo: defining transcriptional networks in adult myogenesis. Nature 4:495–505

Perry RLS, Rudnicki MA (2000) Molecular mechanisms regulating myogenic determination and differentiation. Front Biosci 5:750–767CrossRef

Psilander N, Damsgaard R, Pilegaard H (2003) Resistance exercise alters MRF and IGF-I mRNA content in human skeletal muscle. J Appl Physiol 95:1038–1044PubMed

Rawls A, Morris JH, Rudnicki M, Braun T, Arnold HH, Klein WH, Olson EN (1995) Myogenin’s functions do not overlap with those of MyoD and Myf-5 during mouse embryogenesis. Dev Biol 172:37–50PubMedCrossRef

Rawls A, Valdez MR, Zhang W, Richardson J, Klein WH, Olson EN (1998) Overlapping functions of the myogenin bHLH genes MRF4 and MyoD revealed in double mutant mice. Development 125:2349–2358PubMed

Reimann J, Brimah K, Schröder R, Wernig A, Beauchamp JR, Partridge TA (2004) Pax7 distribution in human skeletal muscle biopsies and myogenic tissue cultures. Cell Tiss Res 315:233–242CrossRef

Reynaud EG, Leibovitch MP, Tintignac LAJ, Pelpel K, Guillier M, Leibovitch SA (2000) Stabilization of MyoD by direct binding to p57^Kip2. J Biol Chem 275:18767–18776PubMedCrossRef

Ridgeway AG, Skerjanc IS (2001) Pax3 is essential for skeletal myogenesis and the expression of Six1 and Eya2. J Biol Chem 276:19033–19039PubMedCrossRef

Riggs JE, Bodensteiner JB, Schochet SS (2003) Congenital myopathies/dystrophies. Neurol Clin N Am 21:779–794

Rudnicki MA, Braun T, Hinuma S, Jaenisch R (1992) Inactivation of MyoD in mice leads to up-regulation of the myogenic HLH gene Myf-5 and results in apparently normal muscle development. Cell 71:383–390PubMedCrossRef

Rudnicki MA, Schnegelsberg PN, Stead RH, Braun T, Arnold HH, Jaenisch R (1993) MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75:1351–1359PubMedCrossRef

Seale P, Sabourin LA, Girgis-Gabardo A, Mansouri A, Gruss P, Rudnicki MA (2000) Pax7 is required for the specification of myogenic satellite cells. Cell 102:777–786PubMedCrossRef

Shimokawa T, Kato M, Ezaki O, Hashimoto S (1998) Transcriptional regulation of muscle specific genes during myoblast differentiation. Biochem Biophys Res Commun 246:287–292PubMedCrossRef

Tajbakhsh S, Rocancourt D, Cossu G, Buckingham M (1997) Redefining the genetic hierarchies controlling skeletal myogenesis: Pax-3 and myf-5 act upstream of MyoD. Cell 89:127–138PubMedCrossRef

Tapscott SJ, Davis RL, Thayer MJ, Cheng PF, Weintraub H, Lassar AB (1988) MyoD1: a nuclear phosphoprotein requiring a Myc homology region to convert fibroblasts to myoblasts. Science 242:405–411PubMedCrossRef

Tseng BS, Cavin ST, Hoffmann EP, Iannaccone ST, Mancias P, Booth FW, Butler IJ (1999) Human bHLH transcription factor gene myogenin (MYOG): genomic sequence and negative mutation analysis in patients with severe congenital myopathies. Genomics 57:419–423PubMedCrossRef

Tzahor E, Kempf H, Mootoosamy RC, Poon AC, Abzhanov A, Tabin CJ, Dietrich S, Lassar AB (2003) Antagonists of Wnt and BMP signalling promote the formation of vertebrate and head muscle. Genes Dev 17:3087–3099PubMedCrossRef

Valdez MR, Richardson JA, Klein WH, Olson EN (2000) Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. Dev Biol 219:287–298PubMedCrossRef

Weintraub H, Tapscott SJ, Davis RL, Thayer MJ, Adam MA, Lassar AB, Miller AD (1989) Activation of muscle-specific genes in pigment, nerve, fat, liver, and fibroblast cell lines by forced expression of MyoD. Proc Natl Acad Sci USA 86:5434–5438PubMedCrossRef

Weintraub H, Davis RL, Tapscott SJ, Thayer M, Krause M, Benezra R, Blackwell TK, Turner D, Rupp R, Hollenberg S, Zhuang Y, Lassar AB (1991) The myoD gene family: nodal point during specification of the muscle cell lineage. Science 251:761–766PubMedCrossRef

Zhang P, Behringer RR, Olson EN (1995) Inactivation of the myogenic bHLH gene MRF4 results in up-regulation of myogenin and rib anomalies. Genes Dev 9:1388–1399PubMedCrossRef

Zhang P, Liegeois NJ, Wong C, Finegold M, Hou H, Thompson JC, Silverman A, Harper JW, DePinho RA, Elledge SJ (1997) Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith–Wiedemann syndrome. Nature 387:151–158PubMedCrossRef

Zhang P, Wong C, Liu D, Finegold M, Harper JW, Elledge SJ (1999) p21^CIP1 and p57^KIP2 control muscle differentiation at the myogenin step. Genes Dev 13:213–224PubMedCrossRef

Title: Myogenin (Myf4) upregulation in trans-differentiating fibroblasts from a congenital myopathy with arrest of myogenesis and defects of myotube formation
Authors: Claudia Weise
Fangping Dai
Felicitas Pröls
Uwe-Peter Ketelsen
Ulrike Dohrmann
Mathias Kirsch
Beate Brand-Saberi
Publication date: 01-11-2006
Publisher: Springer-Verlag
Published in: Brain Structure and Function / Issue 6/2006
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-006-0117-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Myogenin (Myf4) upregulation in trans-differentiating fibroblasts from a congenital myopathy with arrest of myogenesis and defects of myotube formation

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2006

Developmental change of α-gustducin expression in the mouse fungiform papilla

Expression of the avian gene cNOC2 encoding nucleolar complex associated protein 2 during embryonic development

Fos immunoreactivity in some locomotor neural centres of 6OHDA-lesioned rats

Non-neuronal acetylcholine and choline acetyltransferase in oviductal epithelial cells of cyclic and pregnant pigs

The postnatal development of the optic nerve of a reptile (Vipera aspis): a quantitative ultrastructural study

Distribution of calbindin-D28k, neuronal nitric oxide synthase, and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) in the lateral nucleus of the sheep amygdaloid complex