Developmental and Genetic Basis of Neural Circuit Formation and Behavior

Project Summary/Abstract The precise and largely stereotyped connectivity patterns of neurons underlie simple knee-jerk like reflexes and complex behavior, like playing the violin. While we have a good understanding of the conserved genetic and molecular mechanisms that drive the initial steps of nervous system formation, we possess a far more rudimentary knowledge of those that drive neural circuit formation and animal behavior. By focusing on the development and function of the Drosophila adult ventral nerve cord (VNC), which controls behaviors, such as walking, flying, and grooming, our research leverages the power of the fly model system to dissect the genetic and cellular basis of neural circuit formation and behavior. Like the vertebrate spinal cord, the Drosophila adult VNC is composed of segmentally repeated pools of lineally related neurons. In Drosophila, these pools of neurons are termed hemilineages and are the basic developmental and functional unit of the VNC. We have previously mapped the embryonic stem cell origin, axonal projection pattern, transcription factor expression, and neurotransmitter usage of all 34 hemilineages that comprise the adult VNC. In general, however, we lack a clear understanding of the behaviors each hemilineage regulates, the neural circuits within which each hemilineage resides, and most of all the genes that act within each hemilineage to regulate its connectivity and associated behaviors. The goals of this proposal are to elucidate the functions of two conserved transcription factors – the homeodomain-containing protein Hb9 and the Pou-domain containing protein Acj6 – in regulating neuronal connectivity and behavior in each of the six hemilineages in which they are expressed (aim 1), to map each Acj6- or Hb9-positive hemilineage to its associated neural circuit and behavior(s) (aim 2), and to construct a split-GAL4 library that will allow one to uniquely target gene and cell function in every hemilineage in the adult VNC (aim 3). Successful completion of these aims will initiate a systematic dissection of the transcriptional regulatory networks that act within the adult VNC to govern neuronal connectivity and behavior and help build a comprehensive map that links all VNC hemilineages to their associated neural circuits and behaviors. It will also create a genetic toolkit that will allow any lab to dissect gene and cell function in essentially any hemilineage of the adult VNC, facilitating the elucidation of the genetic and cellular basis of behavior. Given the strong parallels between the molecular pathways that govern CNS development in flies and vertebrates, our research holds great potential to uncover conserved genetic principles that underlie neural circuit formation and behavior from flies to humans.