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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 
<http://www.gmu.edu/resources/visitors/findex.html>
 
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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