CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro.
CSX/Nkx2.5 transcription factor plays a pivotal role in cardiac development; however, its role in development and differentiation of other organs has not been investigated. In this study, we used C2C12 myoblasts and human fetal primary myoblasts to investigate the function of Nkx2.5 in skeletal myogenesis. The expression levels of Nkx2.5 decreased as C2C12 myoblasts elongated and fused to form myotubes. The expression of human NKX2.5 in C2C12 myoblasts inhibited myocyte differentiation and myotube formation, and up-regulated Gata4 and Tbx5 expression. The expression of NKX2.5 in terminally differentiated C2C12 myotubes resulted in a change in morphology and breakdown into smaller myotubes. Furthermore, overexpression of NKX2.5 in C2C12 cells and primary cultures of human fetal myoblasts led to differentiation of myoblasts into neuron-like cells and expression of neuronal markers. This study sheds light on the previously unknown non-cardiac functions of Nkx2.5 transcription factor.
Riazi
Ali M
AM
Division of Cardiovascular Surgery Research Rm. 7017, McMaster Bldg., The Hospital for Sick Children, 555 University Ave., Toronto, M5G 1X8 Ontario, Canada. ali.riazi@sickkids.ca
Lee
Haeyul
H
Hsu
Christina
C
Van Arsdell
Glen
G
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D050991:GATA4 Transcription Factor; D049452:Green Fluorescent Proteins / Q000378:metabolism; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000166:cytology*; D009132:Muscles / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
D003470:Culture Media; D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C503799:MYOG protein, human; C503801:Myog protein, mouse; D018008:Myogenin; C484469:Nkx2-5 protein, mouse; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine