Drosophila Cholinergic Neurons

Neuronal Gene Expression We are interested in genes that determine the neuronal cellular fate and specific neurotransmitter phenotypes of cells in the nervous system. The reasons for our interest are two fold. First, identification of the genetic pathways operating in specific types of neurons could explain why they die in neurodegenerative diseases such as Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis. All of these disorders have in common the property that only certain types of neurotransmitter specific neurons degenerate. Secondly, neuronal cell replacement therapies using differentiated stem cell progeny hold the potential to reverse the devastating consequences of neurodegenerative diseases. The genetic personality of specific kinds of neurons must first be defined in order to use proper cells for neuronal replacement and this information will be essential in directing stem cell differentiation into proper developmental pathways. Our current approach to the problems of specification and neurotransmitter phenotype is to create transgenic animals where different neurotransmitter phenotypes are labeled with a fluorescent reporter gene. Labeled neurons are then isolated using Fluorescence Activated Cell Sorting. The purified populations of neurons are analyzed for their whole genome expression patterns using DNA microarray technology. We have successfully applied this approach using Drosophila cholinergic neurons and are now extending our observations to other classes of neurons that use GABA or glutamate as neurotransmitters. Cholinergic neurons express unique sets of ion channels, receptors and other types of genes. We also see unique sets of transcriptional regulatory proteins, and these may be important in the developmental pathways that result in the production of cholinergic neurons. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series