Myogenin can substitute for Myf5 in promoting myogenesis but less efficiently.
The myogenic basic Helix-Loop-Helix transcription factors, including Myf5, MyoD, myogenin (myg) and MRF4, play important roles in skeletal muscle development. The phenotypes of mutant mice deficient in either gene are different, suggesting that each gene may have a unique function in vivo. We previously showed that targeting myogenin into the Myf5 locus (Myf5(myg-ki)) rescued the rib cage truncation in the Myf5-null mutant, hence demonstrating functional redundancy between Myf5 and myogenin in skeletal morphogenesis. Here we present the results of crossing myogenin knock-in (myg-ki) mice with either MyoD-null or myogenin-null mutants. The Myf5(myg-ki) allele rescued early myogenesis, but Myf5(myg-ki/myg-ki);MyoD(-/-) mutant mice died immediately after birth owing to reduced muscle formation. Therefore, myogenin, expressed from the Myf5 locus, is not able to completely replace the function of Myf5 in muscle development although it is capable of determining and/or maintaining myogenic lineage. Myf5(myg-ki/myg-ki);myg(-/-) mutant mice displayed the same phenotype as myg(-/-) mutants. This indicates that the earlier expression of myogenin cannot promote myogenic terminal differentiation, which is normally initiated by the endogenous myogenin. Thus, our results are consistent with the notion that Myf5 and myogenin are functionally interchangeable in determining myogenic lineage and assuring normal rib formation. Our experiment revealed, however, that some aspects of myogenesis may be unique to a given myogenic factor and are due to either different regulatory sequences that control their temporal and spatial expression or different functional protein domains.
Wang
Y
Y
Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.
Jaenisch
R
R
D000483:Alleles; D000818:Animals; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins; D005804:Genes, Lethal; D018257:Helix-Loop-Helix Motifs; D051379:Mice; D008817:Mice, Mutant Strains; D009024:Morphogenesis; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000196:embryology* / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D015534:Trans-Activators; D014157:Transcription Factors