Thesis Defense Announcement
To:  The George Mason University Community

*Candidate: Farheen Shaikh
Program: Master of Science in Biology
*
*Date:   Tuesday January 8, 2013
Time:   11:00 a.m.
Place:  George Mason University, 
	    Fairfax Campus
	   Krasnow Institute, Room 229
*

*Title:  *"The Evolutionary Conserved LIM Homeobox Transcription Factor 
CG4328 Is Required for Dendritic Morphogenesis and Tiling in Drosophila 
Sensory Neurons"**

*Thesis Director*: Dr. Daniel N. Cox**

*Thesis Committee*:  Dr. Geraldine M. Grant and Dr. Alan Christensen

*ABSTRACT *
Nail Patella Syndrome (NPS) is an autosomal dominant disorder, 
characterized by nail malformations, patellar defects, glomerulopathy, 
glaucoma, and a host of neurological disorders. Apart from the 
aforementioned conditions, NPS is also responsible for affecting 
multiple areas of the body. At the molecular level, NPS affects the 
formation of certain proteins. Of particular importance is the product 
of the human /Lmx1b /gene, which is a causative agent in the development 
of this rare autosomal dominant disease. We have previously conducted a 
large-scale /in vivo /RNAi screen to characterize the role of 
transcription factors in mediating class-specific dendrite morphogenesis 
using the /Drosophila /dendritic arborization (da) sensory neurons as a 
model system. From this screen, we identified the gene /CG4328 /which 
encodes a LIM homeodomain transcription factor that is the fly homolog 
of the human /Lmx1b/. RNAi-mediated knockdown of /CG4328 /produced 
significant defects in dendrite morphogenesis and dendritic tiling. 
Based upon these preliminary observations, we performed systematic 
loss-of-function and gain-of-function phenotypic analyses of /CG4328 
/function in mediating da neuron dendrite development and tiling. 
Quantitative analysis reveals that absolute levels of /CG4328/ are 
required for proper dendritic morphogenesis. Altered levels of this 
transcription factor lead to significant reductions in class specific 
dendritic arbor complexity suggesting that /CG4328 /plays an essential 
role in mediating dendritic homeostasis. Moreover, gene expression 
analyses reveal a reduction in expression of genes /cut/, /cubitus 
interruptus /(/ci/) and /elav/ when /CG4328/ levels are altered. The 
results of these analyses indicate that this gene might be involved in 
/hedgehog/ (/hh/) and/or /wingless/ (/wg/) signaling pathways. Further 
analysis may provide novel insight into the mechanisms by which this 
gene, and potentially its human homolog, function to generate the 
neurological defects observed in patients with NPS as, to date, the 
basis for these neurological abnormalities remain poorly understood.

 

A copy of the thesis will be available in the Johnson Center Library.  
All are invited to attend.

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