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Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4.
Dev Biol. 2000 Mar 15; 219(2):287-98.DB

Abstract

The basic helix-loop-helix (bHLH) transcription factors-MyoD, Myf5, myogenin, and MRF4-can each activate the skeletal muscle-differentiation program in transfection assays. However, their functions during embryogenesis, as revealed by gene-knockout studies in mice, are distinct. MyoD and Myf5 have redundant functions in myoblast specification, whereas myogenin and either MyoD or MRF4 are required for differentiation. Paradoxically, myoblasts from myogenin mutant or MyoD/MRF4 double-mutant neonates differentiate normally in vitro, despite their inability to differentiate in vivo, suggesting that the functions of the myogenic bHLH factors are influenced by the cellular environment and that the specific myogenic defects observed in mutant mice do not necessarily reflect essential functions of these factors. Understanding the individual roles of these factors is further complicated by their ability to cross-regulate one another's expression. To investigate the functions of Myf5 in the absence of contributions from other myogenic bHLH factors, we generated triple-mutant mice lacking myogenin, MyoD, and MRF4. These mice appear to contain a normal number of myoblasts, but in contrast to myogenin or MyoD/MRF4 mutants, differentiated muscle fibers fail to form in vivo and myoblasts from neonates of this triple-mutant genotype are unable to differentiate in vitro. These results suggest that physiological levels of Myf5 are insufficient to activate the myogenic program in the absence of other myogenic factors and suggest that specialized functions have evolved for the myogenic bHLH factors to switch on the complete program of muscle gene expression.

Authors+Show Affiliations

Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, 6000 Harry Hines Boulevard, Dallas, Texas, 75235-9148, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10694423

Citation

Valdez, M R., et al. "Failure of Myf5 to Support Myogenic Differentiation Without Myogenin, MyoD, and MRF4." Developmental Biology, vol. 219, no. 2, 2000, pp. 287-98.
Valdez MR, Richardson JA, Klein WH, et al. Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. Dev Biol. 2000;219(2):287-98.
Valdez, M. R., Richardson, J. A., Klein, W. H., & Olson, E. N. (2000). Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. Developmental Biology, 219(2), 287-98.
Valdez MR, et al. Failure of Myf5 to Support Myogenic Differentiation Without Myogenin, MyoD, and MRF4. Dev Biol. 2000 Mar 15;219(2):287-98. PubMed PMID: 10694423.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Failure of Myf5 to support myogenic differentiation without myogenin, MyoD, and MRF4. AU - Valdez,M R, AU - Richardson,J A, AU - Klein,W H, AU - Olson,E N, PY - 2000/3/1/pubmed PY - 2000/3/1/medline PY - 2000/3/1/entrez SP - 287 EP - 98 JF - Developmental biology JO - Dev Biol VL - 219 IS - 2 N2 - The basic helix-loop-helix (bHLH) transcription factors-MyoD, Myf5, myogenin, and MRF4-can each activate the skeletal muscle-differentiation program in transfection assays. However, their functions during embryogenesis, as revealed by gene-knockout studies in mice, are distinct. MyoD and Myf5 have redundant functions in myoblast specification, whereas myogenin and either MyoD or MRF4 are required for differentiation. Paradoxically, myoblasts from myogenin mutant or MyoD/MRF4 double-mutant neonates differentiate normally in vitro, despite their inability to differentiate in vivo, suggesting that the functions of the myogenic bHLH factors are influenced by the cellular environment and that the specific myogenic defects observed in mutant mice do not necessarily reflect essential functions of these factors. Understanding the individual roles of these factors is further complicated by their ability to cross-regulate one another's expression. To investigate the functions of Myf5 in the absence of contributions from other myogenic bHLH factors, we generated triple-mutant mice lacking myogenin, MyoD, and MRF4. These mice appear to contain a normal number of myoblasts, but in contrast to myogenin or MyoD/MRF4 mutants, differentiated muscle fibers fail to form in vivo and myoblasts from neonates of this triple-mutant genotype are unable to differentiate in vitro. These results suggest that physiological levels of Myf5 are insufficient to activate the myogenic program in the absence of other myogenic factors and suggest that specialized functions have evolved for the myogenic bHLH factors to switch on the complete program of muscle gene expression. SN - 0012-1606 UR - https://www.unboundmedicine.com/medline/citation/10694423/Failure_of_Myf5_to_support_myogenic_differentiation_without_myogenin_MyoD_and_MRF4_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0012-1606(00)99621-0 DB - PRIME DP - Unbound Medicine ER -