Positive regulation of myogenic bHLH factors and skeletal muscle development by the cell surface receptor CDO.
Skeletal myogenesis is controlled by bHLH transcription factors of the MyoD family that, along with MEF-2 factors, comprise a positive feedback network that maintains the myogenic transcriptional program. Cell-cell contact between muscle precursors promotes myogenesis, but little is known of the underlying mechanisms. CDO, an Ig superfamily member, is a component of a cell surface receptor complex found at sites of cell-cell contact that positively regulates myogenesis in vitro. We report here that mice lacking CDO display delayed skeletal muscle development. Additionally, satellite cells from these mice differentiate defectively in vitro. CDO functions to activate myogenic bHLH factors via enhanced heterodimer formation, most likely by inducing hyperphosphorylation of E proteins. The Cdo gene is, in turn, a target of MyoD. The promyogenic effect of cell-cell contact is therefore linked to the activity of myogenic bHLH factors. Furthermore, the myogenic positive feedback network extends from the cell surface to the nucleus.
Cole
Francesca
F
Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Zhang
Wei
W
Geyra
Assaf
A
Kang
Jong-Sun
JS
Krauss
Robert S
RS
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002450:Cell Communication; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D019281:Dimerization; D017930:Genes, Reporter; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D019076:Transgenes; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
C107286:CDON protein, human; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D017570:MyoD Protein; D025521:Tumor Suppressor Proteins; D012313:RNA; D010744:Phosphoric Monoester Hydrolases