GDNF Family Ligands in Parasympathetic Neuron Development

Indiana University, Bloomington IN

Investigators

Abstract

The secreted proteins called "neurotrophic factors" exert diverse biological effects on neurons in different developmental contexts, such as differentiation, target innervation, and synaptic specification. Recent studies by our group and others suggest that glial cell line-derived neurotrophic factor (GDNF) and neurturin (NRTN), the two closely related neurotrophic factors, are required for the normal development of several parasympathetic neuron populations and that these proteins are released from target tissues at early embryonic ages. The goal of this project is to elucidate the functional role of GDNF in the generation and differentiation of parasympathetic ciliary ganglion neurons that innervate striate muscle and smooth muscle in the eye. The following three questions will be addressed: (1) Does GDNF promote neurogenesis or neuronal differentiation in the ciliary ganglion? (2) Does GDNF provide a guidance cue for growing ciliary axons? (3) Does GDNF regulate the expression of a proper number of neurotransmitter receptors in ciliary ganglion neurons? Normal functions of GDNF will be manipulated both in vitro and in vivo, and resultant changes in gene expression, protein synthesis, axon outgrowth and receptor localization will be analyzed. These experiments would represent the first systematic attempt to isolate molecular and cellular mechanisms associated with parasympathetic neuron development, and substantially advance our understanding of neuronal identity and specification.