Molecular Biology and Genetics MS Thesis Defense by Filiz Sıla Rızalar

*******************************************************************

KOÇ UNIVERSITY

GRADUATE SCHOOL OF SCIENCES & ENGINEERING

MOLECULAR BIOLOGY AND GENETICS

MS THESIS DEFENSE BY FİLİZ SILA RIZALAR

******************************************************************

Title: Transcription factor CUX1-regulated gene expression in the developing cortex

Speaker: Filiz Sıla RIZALAR

Time: June 19, 2017, 13:00

Place: SCI 103

Koç University

Rumeli Feneri Yolu

Sariyer, Istanbul

Thesis Committee Members:

Asst. Prof. Gülayşe INCE DUNN (Advisor, Koç University)

Asst. Prof. Tuğba BAĞCI ÖNDER (Koç University)

Asst. Prof. Umut ŞAHİN (Boğaziçi University)

Abstract:

Nervous system contains a large variety of cells with different dendritic morphologies, axonal connections, neurotransmitters and gene expression patterns. Diverse intercellular signaling mechanisms, temporally regulated factors and intrinsic cues play important roles in the generation of this complex system. The cerebral cortex, which instructs higher order sensory, cognitive and motor functions, is organized into six functional layers. Certain transcription programs intrinsically regulate the positioning and layer identity of cortical neurons. Cux1 (Cut-like homeobox 1) gene encodes a homeodomain transcription factor which regulates the differentiation and physiology of layer II-III cortical neurons by inducing dendritic branching, increasing the number and the density of dendritic spines and modulating synaptogenesis. It also regulates the formation of corpus callosum axon tract which facilitates the connection between two hemispheres. There is a lack of comprehensive data on the genome-wide targets of CUX1 through which it maintains layer identity in cortical neurons. Studies aimed to identify these gene targets are currently limited to in vitro experiments on non-neuronal cell lines. In this study, I have identified the genome-wide binding profiles and target genes of CUX1 homeodomain transcription factor by chromatin immunoprecipitation followed by sequencing (ChIP-Seq) experiment in the developing mouse cerebral cortex. My results revealed that CUX1 transcription factor regulates excitatory synapses by direct binding to a set of genes that regulate glutamatergic signaling. CUX1 also targets several genes regulating axon guidance, a portion of which are responsible for formation and regulation of corpus callosum axon tract.