The experiments which we are proposing will test the ability of muscle stem cells to survive transplantation, to colonize or augment host muscle to reverse the effects of genetically-induced alterations in the integrity and life span of muscle, and to become immortal. Classic experiments by Hadorn and others in Drosophila melanogaste have shown that the epithelial (cuticle- forming) cells associated with the imaginal disks of the presumptive adult appendages can be immortalized by culturing them in the abdomens of adult hosts. This isolates them from the hormonal cues that induce metamorphic cell differentiation. These cultured imaginal disks can then be induced to differentiate normally, months or even years later, by transplanting them into late-larval hosts and allowing them to undergo metamorphosis. The recent development of techniques for marking Drosophila cells with biochemical tags will enable us to determine whether the life span of the adepithelial cells (adult muscle precursors) within the disks can be similarly prolonged by transplantation.
The first aim of this project will be to follow the fates of these muscle stem cells as they are transplanted into successive hosts and to determine whether the differentiation of normal adult muscle stem-cell populations can be retarded or accelerated.
Our second aim will be to test the ability of the transplanted myoblasts to reverse the effects of genetic mutations which delete a single specific muscle or cause it to degenerate prematurely. We will screen hosts for behavioral and physiological recovery of function, and individually mark and evaluate the activity of their motorneurons. The out come of these experiments should also help to answer our third aim: to determine whether it is defects in the muscles or in the neurons innervating the muscles that are responsible for the muscle deletions.
