The long term objective of this research is to understand the molecular mechanisms that direct the migration of myoblasts. The ability of myoblasts to migrate to specific positions is crucial for the normal development and repair of muscle. It is not well understand how myoblasts are guided to migrate to their proper sites. Knowledge about the mechanisms involved in directing migration will aid our understanding of congenital defects in muscle development and will bear upon gene therapies that rely on myoblast transplantation. In Drosophila, male fertility depends upon the precise migration of myoblasts to the gonad, where they will form a muscle that ensheathes the testis. This migratory event is an excellent model to study the signals that induce myoblast migration. Dwnt- 2, a member of the family of secreted Wnt proteins, is one signal necessary for the formation of the testis muscle, but its role in this process is unclear. Wnt signals have crucial developmental functions, including the patterning of the central nervous system and the somites, but have not previously been assigned a role in myoblast migration. One objective of this proposal is to determine whether Dwnt-2 acts through a direct effect on myoblasts.. The identification of Dwnt-2 as a signal directly involve din the induction of myoblast migration would provide an avenue for further study of the signaling mechanism involved. Defects in testis muscle development have been observed in a second Drosophila mutant, and this proposal details a plan to identify the gene that is responsible. The similarity of this phenotype to that of the Dwnt-2 mutant suggests that these genes might act in the same pathway. To fully elucidate the signaling pathways that are involved in myoblast migration, we aim to identify other genes that are required for myoblast migration. To achieve this, a large collection of existing male sterile mutants will be examined to identify those with defects in the migration of testis muscle precursors. Additionally, enhancer detector lines will be examined to identify genes whose expression patterns indicate their potential involvement in myoblast migration.
| Kozopas, Karen M; Nusse, Roel (2002) Direct flight muscles in Drosophila develop from cells with characteristics of founders and depend on DWnt-2 for their correct patterning. Dev Biol 243:312-25 |
