NEUROD2 yazılım faktörü'nün genom hedef analizi kortikal göç ve tabaka oluşumundaki potansiyel rolleri ortaya çıkarır

Specialized functions of cells and how they communicate with each other determine the functions of organs as well as organ systems. The nervous system consists of the brain, spinal cord and the peripheral nerves of the body and it allows an organism to perceive and respond to the environment. The brain is a complex organ that is composed of complex networks of neurons. Each neuron receives input from thousands of other neurons, so trillions of connections are created in the brain. This intricacy provides us to perform many sensory, motor and cognitive tasks. Different types of transcription regulators play roles in the development of the nervous system. Prominent among them are the basic helix-loop-helix (bHLH) family of transcription factors that control a wide array of developmental process in different organisms. Neurogenic Differentiation Factor2 (NeuroD2), a member of the neurogenic bHLH transcription factors, contributes to neurogenesis significantly in the brain. The complexity of the gene regulatory system that controls the development of the rich assortment of neurons is revealed by the identification of direct target genes of transcription factors. Despite the crucial role of NeuroD2 in neuronal differentiation and development, its transcriptional downstream target genes during development are not known. My goal in this study was to analyze the binding profiles of NeuroD2 transcription factor in whole genome as revealed by a previous Chromatin Immunoprecipitation followed by sequencing (ChIP-Seq) experiment conducted in our laboratory. My results demonstrated that NeuroD2 regulates a set of genes which are responsible for axon guidance, synaptogenesis, neuronal migration; cortical layer identity and dendritogenesis. Further I aimed to analyze the function of NeuroD2 in the dendrite development and branching; however I found that NeuroD2 does not affect the morphology of dendrites in primary cortical neurons. In addition, I examined the mechanism by which NeuroD2 regulates the Inhibitor of Differentiation 2 (Id2) protein which inhibits E-box mediated gene expression by interfering with binding of neurogenic bHLH proteins to their target promoters. My results showed that the mRNA level of Id2 does not change in the knockdown of NeuroD2 suggesting that NeuroD2 does not regulate the expression of Id2 gene at the conditions examined. Taken together, my findings indicate that NeuroD2 is an effector transcription factor that targets key genes playing role in cortical migration and layer formation and required for major signaling pathways such as Reelin and Wnt pathways while it is not necessary for the dendrite morphology and regulation of Id2 gene expression.