TY - JOUR T1 - A cellular and regulatory map of the GABAergic nervous system of <em>C. elegans</em> JF - bioRxiv DO - 10.1101/052431 SP - 052431 AU - Marie Gendrel AU - Emily G. Atlas AU - Oliver Hobert Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/05/10/052431.1.abstract N2 - The nervous system of the nematode C. elegans is the only nervous system with a complete “parts list” and a complete wiring diagram. Neurotransmitter maps are important complements to such anatomical maps and represent an invaluable resource that will help to understand how signals are transmitted throughout the nervous system and how a nervous system is developmentally patterned. In this resource paper, we report a comprehensive map of neurons in the hermaphroditic and male C. elegans nervous system that contain the neurotransmitter GABA, the most prominent inhibitory neurotransmitter in mammalian nervous systems. We reveal twice as many GABA-positive neuron classes as previously reported, several of them also cotransmitting acetylcholine. We define previously unknown glia-like cells that reuptake GABA, as well as “GABA reuptake neurons” which do not synthesize GABA but take it up from the extracellular environment. One GABA reuptake neuron type may clear GABA thereby possibly modulating GABAergic neurotransmission (“GABA clearance” neuron), while another GABA reuptake neuron type may re-release GABA (termed “GABA recycling” neuron). We used the map of GABA-positive neurons for a comprehensive analysis of transcriptional regulators that define the GABA phenotype. We show that nine transcription factors operate in specific combinations to control GABAergic identity of most GABAergic neuron classes. Among these factors is elt-1, the C. elegans ortholog of GATA2/3, a selector gene of GABAergic identity of several distinct types of GABAergic neurons in vertebrates. Other factors that control GABAergic identity include the Tlx-type nuclear hormone receptor nhr-67 which controls the identity of four distinct GABAergic neuron classes, in which, depending on neuron type, nhr-67 cooperates with three different types of homeobox genes. We also identified homeobox genes that specify GABA recycling neurons and GABA clearance neurons. The regulators of GABAergic neuron identity do not only specify neurotransmitter identity, but multiple other identity features as well. We synthesize our findings of specification of GABAergic neurons with previous reports on the specification of glutamatergic and cholinergic neurons into a nervous system-wide regulatory map which defines neurotransmitter specification mechanisms for more than half of all neuron classes in C. elegans. ER -