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.