Differential control of cell death and gene expression during two distinct phases of hormonally-regulated muscle death in the tobacco hawkmoth Manduca sexta.

In larvae of the tobacco hawkmoth Manduca sexta, the intersegmental muscles (ISMs) span eight abdominal segments and represent the major muscle group. Following pupation, the ISMs in the first two and last two segments undergo programmed cell death (PCD), while the remaining four segments persist until the time of adult eclosion, when they too undergo PCD. ISM death at adult eclosion is initiated by a decline in the circulating ecdysteroid titer and requires de novo gene expression. In this study we have investigated the hormonal regulation and the patterns of gene expression that accompany both early and late ISM death. We find that distinct endocrine cues regulate these two periods of muscle death. Even though the middle segments of ISMs are exposed to the same endocrine environment as the adjacent cells that die following pupation, they do not express death-associated transcripts until they are specifically signaled to die following adult eclosion. These data indicate that subsets of homologous muscles appear to make segment-specific decisions to couple their endogenous cell death programs to distinctly different developmental cues. Nevertheless, once cell death is initiated, they utilize many of the same molecular components.

Loss of myogenin in postnatal life leads to normal skeletal muscle but reduced body size.

Although the mechanisms regulating the formation of embryonic skeletal muscle in vertebrates are well characterized, less is known about postnatal muscle formation even though the largest increases in skeletal muscle mass occur after birth. Adult muscle stem cells (satellite cells) appear to recapitulate the events that occur in embryonic myoblasts. In particular, the myogenic basic helix-loop-helix factors, which have crucial functions in embryonic muscle development, are assumed to have similar roles in postnatal muscle formation. Here, we test this assumption by determining the role of the myogenic regulator myogenin in postnatal life. Because Myog-null mice die at birth, we generated mice with floxed alleles of Myog and mated them to transgenic mice expressing Cre recombinase to delete Myog before and after embryonic muscle development. Removing myogenin before embryonic muscle development resulted in myofiber deficiencies identical to those observed in Myog-null mice. However, mice in which Myog was deleted following embryonic muscle development had normal skeletal muscle, except for modest alterations in the levels of transcripts encoding Mrf4 (Myf6) and Myod1 (MyoD). Notably, Myog-deleted mice were 30% smaller than control mice, suggesting that the absence of myogenin disrupted general body growth. Our results suggest that postnatal skeletal muscle growth is controlled by mechanisms distinct from those occurring in embryonic muscle development and uncover an unsuspected non-cell autonomous role for myogenin in the regulation of tissue growth.