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 and nervous system disease pathologies.

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, including dendritic tiling, of critical importance to the formation of functional neural networks.

Key areas of inquiry in this field include:

  1. the mechanisms by which the size, shape and complexity of dendritic arbors is achieved and subsequently regulated at a class-specific neuron level

  2. how the boundaries of neuronal receptive fields are specified and refined

  3. how dendrites function in mediating recognition between synaptic partners

  4. how dendritic fields are established, maintained and remodeled during development

We use developmental neurogenetics, cell biology, high-resolution confocal imaging, and genomics to dissect the molecular mechanisms mediating class specific dendrite morphogenesis. The Drosophila peripheral nervous system (PNS) serves as a molecular, genetic, morphological and behavioral model system in which to investigate these processes. 

Current Projects

Presently, we are focused on transcriptional, cytoskeletal, cell surface receptor, and small RNA (siRNA/miRNA) regulatory mechanisms governing class-specific dendrite morphogenesis as they relate to dendritic field specification and dendritic tiling. 

We have also developed novel methods for the isolation of class-specific neurons via magnetic bead cell sorting and laser capture microdissection. We have applied these cell isolation methods to conduct microarray transcriptome analyses of class-specific neuron development in both wild-type and mutant (LOF/GOF) genetic backgrounds. To validate our microarray studies, we have conducted large scale in vivo RNAi-based phenotypic screens which have revealed a broad range of transcriptional regulatory mechanisms underlying distinct aspects of class-specific dendrite morphogenesis, many of which are under active investigation.



Funding Agencies

National Institutes of Health
The Thomas F. & Kate Miller Jeffress Memorial Trust
George Mason University Foundation

Media Coverage

George Mason University News: Cox Lab news

 

Research

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