CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro

Ali M Riazi; Haeyul Lee; Christina Hsu; Glen Van Arsdell

doi:10.1074/jbc.M500028200

CSX/Nkx2.5 modulates differentiation of skeletal myoblasts and promotes differentiation into neuronal cells in vitro

J Biol Chem. 2005 Mar 18;280(11):10716-20. doi: 10.1074/jbc.M500028200. Epub 2005 Jan 13.

Authors

Ali M Riazi¹, Haeyul Lee, Christina Hsu, Glen Van Arsdell

Affiliation

¹ 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

PMID: 15653675
DOI: 10.1074/jbc.M500028200

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenoviridae / genetics
Animals
Blotting, Western
Bromodeoxyuridine / pharmacology
Cell Cycle
Cell Differentiation
Cell Line
Cell Nucleus / metabolism
Cells, Cultured
Culture Media / pharmacology
DNA-Binding Proteins / biosynthesis
GATA4 Transcription Factor
Green Fluorescent Proteins / metabolism
Homeobox Protein Nkx-2.5
Homeodomain Proteins / metabolism
Homeodomain Proteins / physiology*
Humans
Immunoprecipitation
Mice
Microscopy, Fluorescence
Muscle, Skeletal / cytology*
Muscles / cytology
Muscles / embryology*
Muscles / metabolism
Myogenin / metabolism
Neurons / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
T-Box Domain Proteins / biosynthesis
Transcription Factors / biosynthesis
Transcription Factors / metabolism
Transcription Factors / physiology*
Up-Regulation

Substances

Culture Media
DNA-Binding Proteins
GATA4 Transcription Factor
Homeobox Protein Nkx-2.5
Homeodomain Proteins
MYOG protein, human
Myog protein, mouse
Myogenin
Nkx2-5 protein, mouse
T-Box Domain Proteins
T-box transcription factor 5
Transcription Factors
Green Fluorescent Proteins
Bromodeoxyuridine