Genetic Dissection of L1-type Neural Cell Adhesion Molecules in a Developing Nervous System

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Abstract: Cell surface proteins of the L1 family of cell adhesion molecules are centrally involved in numerous developmental processes, especially during the formation of the nervous system. They interact with a large number of different proteins on the outside, as well the inside of cells that express such molecules. Whereas some functional properties of L1 proteins are well conserved in a wide range of species, from nematodes to humans, other functions and binding partners have been developed more recently during evolution. The proposed research tries to dissect this functional complexity of L1 proteins by analyzing the structural and functional requirements for L1-type proteins in specific developmental processes. The research plan will focus on the formation of the nervous system in the fruitfly Drosophila melanogaster. Mutant Drosophila embryos that do not express any L1-type proteins die and exhibit many subtle abnormalities in their developing nervous system and a number of other tissues. In Drosophila embryos with mutations in their L1-type gene, several nerves are not appropriately formed and specific neuronal cells are unable to make the correct cellular connections with their targets. Natural, as well as artificially altered and mutant L1-type proteins will be reintroduced into such embryos to test whether they are able to rescue specific neurological malformations that are caused by the absence of the endogenous Drosophila L1 protein. This analysis will shed light on what molecular functions and interactions of L1-type proteins are required in which types of cells to support certain developmental processes.