Cellular and molecular functions and signalling mechanisms of Nel

The brain contains an orderly and stereotyped network of nerve cells, and correct functioning of the brain is critically dependent on the proper formation of the neuronal network. In human, for example, it is estimated that about one billion nerve cells form more than one quadrillion specific connections. During development of the neuronal network, nerve fibres must follow the defined pathways and project to the correct targets. In this process, nerve fibres are guided by external molecular cues derived from their pathways and targets. Guidance cues are recognized by nerve fibres through specific 'receptors'. Therefore, studies on the interaction between guidance molecules and their receptors are a key to the elucidation of molecular mechanisms of brain development. The proposed research focuses on a protein called Nel. Although Nel exists in the developing nervous system and has structural features that are found in other molecules that play important biological functions, little is known about its functions in development of the nervous system. In addition, the receptor(s) for Nel has not been identified. Our preliminary studies have already indicated that Nel is a novel axon guidance cue in the visual system. In the proposed research, we will analyze the functions of Nel in development of the visual system and identify its receptor. We expect that the proposed research will reveal the function of Nel in neuronal network formation and the molecular mechanism by which Nel controls behaviour of nerve fibres. In addition, results from this project will have major clinical implications for strategies aimed at neuronal regeneration after brain and spinal cord injuries and for treatment of birth defects affecting the nervous system.