Survival motor neuron protein deficiency impairs myotube formation by altering myogenic gene expression and focal adhesion dynamics

• Published in: Human molecular genetics Vol. 23; no. 18; pp. 4745 - 4757
• Main Authors: Bricceno, Katherine V, Martinez, Tara, Leikina, Evgenia, Duguez, Stephanie, Partridge, Terence A, Chernomordik, Leonid V, Fischbeck, Kenneth H, Sumner, Charlotte J, Burnett, Barrington G
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 15-09-2014
• Subjects: Animals; Cell Differentiation; Cell Line; Cell Movement; Focal Adhesions - metabolism; Gene Expression Regulation; Humans; Mice; Muscle Development; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; MyoD Protein - genetics; MyoD Protein - metabolism; Myogenin - genetics; Myogenin - metabolism; PAX7 Transcription Factor - genetics; PAX7 Transcription Factor - metabolism; Survival of Motor Neuron 1 Protein - genetics; Survival of Motor Neuron 1 Protein - metabolism
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddu189

While spinal muscular atrophy (SMA) is characterized by motor neuron degeneration, it is unclear whether and how much survival motor neuron (SMN) protein deficiency in muscle contributes to the pathophysiology of the disease. There is increasing evidence from patients and SMA model organisms that SMN deficiency causes intrinsic muscle defects. Here we investigated the role of SMN in muscle development using muscle cell lines and primary myoblasts. Formation of multinucleate myotubes by SMN-deficient muscle cells is inhibited at a stage preceding plasma membrane fusion. We found increased expression and reduced induction of key muscle development factors, such as MyoD and myogenin, with differentiation of SMN-deficient cells. In addition, SMN-deficient muscle cells had impaired cell migration and altered organization of focal adhesions and the actin cytoskeleton. Partially restoring SMN inhibited the premature expression of muscle differentiation markers, corrected the cytoskeletal abnormalities and improved myoblast fusion. These findings are consistent with a role for SMN in myotube formation through effects on muscle differentiation and cell motility.