Chapter 19: Molecular genetic specification of cholinergic neurons

Abstract

Publisher Summary The nervous system is a patterned collection of cells exhibiting a variety of specific chemical phenotypes. This chapter is interested in the molecular genetic specification, maintenance, and functional significance of the cholinergic neurons. Neurons are cholinergic if they make and use acetylcholine as a neurotransmitter. They can attain this chemical phenotype by expressing the gene for choline acetyltransferase, the biosynthetic enzyme catalyzing acetylcholine production. An advantage of using Drosophila is that, it is one of the few species where mutant alleles for the ChAT gene are known. It may thus be possible to assign behavioral, physiological, and cellular phenotypes to the presence of a mutant allele. The type of ChAT regulation inferred from the reporter gene studies indicates that various subsets of cholinergic neurons are specified, at least in part, by regulatory sequences present in the genome. These regulatory motifs can interact with various combinations of transcription factors, and result in either inhibition or activation of ChAT gene expression. This type of molecular genetic logic leads to the interesting idea that the cholinergic neurons present in different parts of the nervous system, and presumably with different functional roles, may be specified by separable regulatory elements. This chapter also attempts to test this idea by rescuing mutant phenotypes of animals that carry a mutant endogenous ChAT gene. Phenotype rescue is accomplished by using various 5’ flanking DNA to drive expression of wild type ChAT in specific subsets of cholinergic neurons in animals with a mutant ChAT background.