Grant: Discovery Grants Program - Individual

My research program focusses on how nerve cells extend their processes during development and nerve regeneration and then form connections with appropriate partner cells. To this end, I use the large identifiable nerve cells of the adult mollusc, Lymnaea stagnalis, which can regenerate in cell culture. At the growing ends of regenerating neurites, structures known as growth cones are found. These structures are responsible for pathfinding during nervous system development and regeneration, and then selecting and forming appropriate connections with target cells. This research proposal focusses on the role of the Vitamin A metabolite, known as retinoic acid, in nerve outgrowth and growth cone behaviour during regeneration in the adult nervous system. Retinoic acid is well known to play important roles in vertebrate nervous system development, but less is known about its effects on regeneration. In this application, we propose to study the mechanisms underlying the actions of retinoic acid in guiding growth cones and to investigate the interactions between retinoic acid and other guidance molecules, such as the transmitter, dopamine. In addition, we will determine how changes in growth cone behaviour might affect the choice of synaptic partners. These experiments will be carried out using cell culture techniques. We also propose to study the effects of retinoic acid on regeneration of different identifiable cell-types within the nervous system, using the intact brain and intact animal nerve-crush preparations. These studies will be significant in advancing our understanding of the effects of retinoic acid both in the developing and regenerating nervous system. A basic understanding of how retinoic acid affects the nervous system will ultimately have implications for use of retinoid therapies and increased understanding of diseases such as Vitamin A deficiency.