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Dissertation Defense Announcement
To:  The George Mason University Community

Candidate: Vincent Hermoso
Program:    PhD Biosciences

Date:   Tuesday April 24, 2012
Time:   10:00 a.m.
Place:   George Mason University
             Research I, Room 161
             Fairfax campus
 
Dissertation Director: Dr. Daniel N. Cox
Committee members: Dr. Geraldine Grant, Dr. Alan Christensen, Dr. Nadine Kabbani
Title: "Characterization of arbor defective, a novel immunoglobulin superfamily molecule required for dendrite morphogenesis in Drosophila"


The dissertation is on reserve in the Johnson Center Library, Fairfax campus.
The doctoral project will not be read at the meeting, but should be read in advance.

All members of the George Mason University community are invited to attend.


ABSTRACT:


Dendrites function as the primary sites of synaptic and/or sensory input and integration within the developing nervous system. The initiation and subsequent maintenance of dendritic branches determine both the number and type of inputs they receive and are thus critical in establishing functional neural networks. However, our understanding of the molecular bases governing the acquisition of class specific dendritic morphologies remains far from complete.  Due to their pivotal role in neural function, elucidating the molecular mechanisms underlying dendrite morphogenesis is the key to understanding how different neuronal subtypes influence neural activity and development.
This thesis focuses primarily on the molecular, genetic, and biochemical characterization of a novel, evolutionarily conserved, putative cell adhesion molecule dubbed arbor defective (arbd) based upon defects observed in mutant animals with respect to dendrite arborization.  Arbd is member of the immunoglobulin superfamily (IgSF) proteins. These proteins share common structural domains and have been widely implicated as cell surface receptors and cell adhesion molecules.  As a member of the IgSF, Arbd shares close homology and domain organization with a number of nervous system-specific IgSF proteins including its closest Drosophila orthologue, turtle (tutl).  
Using a multi-disciplinary in vivo genetic and proteomic approach, the molecular mechanisms by which arbd contributes to the regulation of class-specific dendrite development was investigated.  Immunohistochemistry studies revealed that Arbd protein is specifically expressed on the cell surface of all dendritic arborization (da) neurons of the Drosophila peripheral nervous system (PNS).  Loss-of-function phenotypic analyses revealed that arbd is required in da neuron sublcasses to promote normal dendritic branching complexity as well as dendritic extension/growth.  In contrast, gain-of-function overexpression analyses of arbd revealed class-specific effects on da neuron dendritogenesis suggesting potential context-dependent regulatory mechanisms via which this gene directs dendrite development.  Trans-heterozygous loss-of-function mutant analyses of arbd and tutl revealed compensatory and synergistic interactions in da neuron subclasses suggesting that these two highly related IgSF proteins may genetically interact in regulating class-specific dendritogenesis.  To gain insight into the molecular mechanisms by which Arbd regulates dendrite morphogenesis, a proteomics approach was used to identify Arbd-interacting proteins.  These studies revealed two protein interactors including Crinkled, a myosin VIIA motor protein, and Rab3-GAP, a GTPase activating protein that regulates the small GTPase Rab3.  Phenotypic analyses of mutants for these two molecules revealed defects in da neuron dendrite development that largely phenocopy those defects observed in arbd mutants suggesting that Arbd may function in a common signaling pathway with Crinkled and Rab3-GAP.

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