The goals of the proposed studies are designed to provide new insight into the molecular and regulatory mechanisms governing the acquisition of class-specific dendritic morphologies. Class-specific dendrite arborization patterns serve as a hallmark of neuronal type and moreover, it is this stereotypic branching pattern that defines a neuron's receptive field determining both the number and type of synaptic or sensory inputs that neuron is capable of receiving and responding to making dendritic field specification, of critical importance to the formation of functional neural networks. While our broad understanding of dendrite arborization and dynamics has made substantial progress in recent years, the molecular and cellular mechanisms governing these processes in vivo remain largely unknown. Our focus has been to address these questions in the Drosophila peripheral nervous system using a class of sensory dendrite arborization (da) neurons that provide an excellent model system for the analyses of these processes. Specifically, we propose to:
AIM I. Investigate the functional role(s) of the turtle gene in mediating class-specific PNS dendrite morphogenesis through expression studies and phenotypic analyses of both loss-of-function and gain-offunction ectopic/over-expression mutants. (Years 1-2) AIM II. Dissect potential regulatory interactions between turtle and the homeodomain transcription factor, cut, through in vivo genetic manipulations and in vitro biochemical studies. (Years 1-2) AIM III: Identification and characterization of downstream effectors mediating cut transcriptional regulation of class-specific dendrite morphogenesis (Years 1-3) Collectively, these studies have the potential to provide novel insight into the molecular and regulatory mechanisms governing the acquisition of class-specific dendritic morphologies. Moreover, given the functional conservation between Drosophila and vertebrates for genes such as turtle and cut, (Shi et al., 2004a;Grueber et al., 2003a), these studies may provide intriguing entry points for extending the findings obtained in Drosophila via translational studies in vertebrate model systems.
Dendrites function as the primary sites of synaptic and/or sensory input and integration in the developing nervous system, thus, elucidating the molecular mechanisms governing dendrite morphogenesis is critical to our understanding of how diverse cell-type specific dendritic morphologies arise and further, how these morphologies may be affected in such biologically relevant events as sensory perception, learning and memory, aging, addiction, and a broad range of nervous system disease pathologies, including Alzheimer's disease and mental retardation. Despite this functional importance, to date, little is known of the molecular mechanisms regulating cell-type specific dendrite development.
Showing the most recent 10 out of 14 publications
