A long-term goal of this research is to identify molecular mechanisms that control axon guidance across the midline in the developing Drosophila ventral nerve cord. Axons traversing the midline, called commissural axons, establish a critical link required for information transfer between the left and right sides of the body. Pioneer trajectories early in development lay the foundation and generate the scaffolding upon which the mature nervous system is subsequently built. Our laboratory has identified a novel member of the receptor tyrosine kinase family, called Derailed 2 (Drl2). Given it?s strong sequence homology to Derailed (Dri), a gene with an established role in midline commissure choice, as well as in situ data which localizes Drl2 transcripts to the midline, we feel Drl2 is an excellent candidate molecule for potential function in midline guidance. The proposed research will be focused upon the determination of the precise expression pattern and function of this new gene. This goal will be achieved through the use of the following design and methods: 1. Use of tau-based reporters under the control of Drl2 regulatory sequences and specific antibodies to reveal the identity of Drl2-expressing neurons, 2. use of the Ga14/UAS transactivation system to ectopically express Drl2, and 3. screens for Drl2 loss-of-function mutations to assess functional consequences. The clinical relevance of basic developmental studies in model systems is underscored by repeated demonstrations of interphyletic conservation of fundamental developmental programs.
