Graduate Program in Molecular Biology and Genetics.Çelik, Arzu.Oruç, Eymen Ece.2025-04-142025-04-142023Graduate Program in Molecular Biology and Genetics. PSY 2023 B56 PhD (Thes CMPE 2023 C34https://digitalarchive.library.bogazici.edu.tr/handle/123456789/21629Intellectual disability (ID) is defined as general deprivation in cognition and learning, affecting around 1-2% of people worldwide. Although the underlying causes of ID are numerous and complex, there is a convergence in mechanisms that are affected. Intracisternal A particle-promoted polypeptide (IPP) gene encodes for 584amino acid-long IPP protein that includes a BTB/POZ domain, a BTB/Kelch associated domain and 6 Kelchrepeat domains. The Kelch protein family is known to be essential for maintaining the actin organization. There have been 63 members identified in the Kelch protein superfamily and several of them have been associated with intellectual disability. Drosophila melanogaster provides numerous advantages in modelling human brain diseases due to its short life span, large number of offspring and ease of genetic manipulation with currently available techniques. CG9426 is the Drosophila ortholog of the IPP gene sharing 37% identity and 58% similarity. My aim was to analyze the morphological outcomes of dysregulation of IPP by using Drosophila melanogaster as a model organism and obtain a broader perspective on IPP. In this study I demonstrated how IPP expression compensated for the low viability rate and reduced the ratio of mushroom body defects in CG9426 knockout mutants. These results support the idea that CG9426 and IPP are functional orthologs, and Drosophila melanogaster can be a suitable model to understand the causative of role of IPP in intellectual disability. The expression pattern of CG9426 was analyzed and found to be expressed in neuroblasts in the larval brain and glial cells in the adult fly brain. Glial cells have an equally important role in nervous system function as their neuronal counterparts. The attributed roles of glia range from controlling neuronal cell number and axonal pathfinding to regulating synapse formation, function, and plasticity. CG9426 knockout and knockdown lines exhibited defects in their mushroom bodies highlighting the importance of IPP and its fly ortholog in neurodevelopment.Intellectual disability -- Diagnosis.Drosophila -- Genetics.Nervous system.xviii, 115 leaves