MYOGENIN IS REQUIRED, FOR LATE BUT NOT EARLY ASPECTS OF MYOGENESIS DURING MOUSE DEVELOPMENT

Mice with a targeted mutation in the myogenic basic helix-loop-helix r egulatory protein myogenin have severe muscle defects resulting in per inatal death, In this report, the effect of myogenin's absence on embr yonic and fetal development is investigated, The initial events of som ite differentiation occurred normally in the myogenin-mutant embryos. During primary myogenesis, muscle masses in mutant embryos developed s imultaneously with control siblings, although muscle differentiation w ithin the mutant muscle masses was delayed, More dramatic effects were observed when secondary myofibers form. During this time, very little muscle formation took place in the mutants, suggesting that the absen ce of myogenin affected secondary myogenesis more severely than primar y myogenesis, Monitoring mutant neonates with fiber type-specific myos in isoforms indicated that different fiber types were present in the r esidual muscle, No evidence was found to indicate that myogenin was re quired for the formation of muscle in one region of the embryo and not another. The expression patterns of a MyoD-lacZ transgene in myogenin -mutant embryos demonstrated that myogenin was not essential for the a ctivation of the MyoD gene. Together, these results indicate that late stages of embryogenesis are more dependent on myogenin than early sta ges, and that myogenin is not required for the initial aspects of myog enesis, including myotome formation and the appearance of myoblasts.