Project 170990

The human central nervous system (CNS) is comprised of cells of two major classes, neurons and glial cells. Interactions between them are vital for the CNS to develop and function properly, but little is known of the molecular mechanisms by which this occurs. Disruption of neuron-glial interactions may underlie a number of human diseases. The van Meyel laboratory uses a simple organism - the fruit fly Drosophila - to better understand molecular and cellular interactions between neurons and glia during development. Drosophila has been well-studied and has proven to be a useful genetic model for many avenues of biomedical research. Neurons and glial cells in the Drosophila CNS display many of the same molecular and functional properties as neurons and glia in humans. To study glial cell differentiation and neuron-glial interactions, we focus on an interesting subtype of Drosophila glia called the longitudinal glia (LG). We found that communication between neurons and LG occurs through a particular molecular signaling pathway mediated through the Notch receptor molecule. This receptor's signaling pathway is also important for glial cell differentiation during nervous system development in mammals. We will use genetic studies in Drosophila to better understand mechanisms by which glial cells contribute to human nervous system development, function and disease. By studying LG, we will first identify additional molecules that also participate in glial cell development and differentiation. Second, we will study how the Notch receptor influences the development and differentiation of these glial cells. Third, we have developed a Drosophila model for episodic ataxia in humans. Using this model, we will study how LG can influence the function of connections between neurons that are important for locomotion.

using a Drosophila model to study glial cell differentiation and neuron-glial interactions in the CNS