Pro- and anti-apoptotic members of the Bcl-2 family in skeletal muscle: A distinct role for Bcl-2 in later stages of myogenesis

Apoptotic myonuclei appear during myogenesis and in diseased muscles. To in vestigate cell death regulation in skeletal muscle, we examined how members of the Bcl-2 family of apoptosis regulators are expressed and function in the C2C12 muscle cell. line and in primary muscle cells at different stages of development. Both anti-apoptotic (Bcl-W, Bcl-X-L) and pro-apoptotic (Ba d, Bak, Bax) members of the Bcl-2 family were expressed in developing skele tal muscle in vivo. Each was also expressed in embryonic (E11-12), fetal (E 15-16), and neonatal muscle stem cells, myoblasts, and myotubes in vitro. I n contrast, Bcl-2 expression was Limited to a small group of mononucleate, desmin-positive, myogenin-negative muscle cells that were seen in fetal and neonatal, but not embryonic, muscle cell cultures. The cell surface protei n Sca-1, which is associated with muscle and blood stem cells, was found on similar to1/2 of these Bcl-2-positive cells. Loss of Bcl-2 did not affect expression of other family members, because neonatal muscles of wild-type a nd Bcl-2-null mice had similar amounts of Bcl-X-L, Bcl-W, Bad, Bak, and Bax mRNAs. Loss of Bcl-2 did have functional consequences; however, because ne onatal muscles of Bcl-2-null mice had only similar to2/3 as many fast muscl e fibers as muscles in wild-type mice. Thus, Bcl-2 function is required for particular stages of fetal and postnatal myogenesis. (C) 2001 Wiley-Liss, Inc.