Investigating the Role of Target of Rapamycin (TOR) Signaling Pathway in Border Cell Migration during Drosophila Oogenesis

Biju, Neha (2022) Investigating the Role of Target of Rapamycin (TOR) Signaling Pathway in Border Cell Migration during Drosophila Oogenesis. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS dissertation of Neha Biju (17MS013)) 17MS013_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

Collective cell migration is the coordinated motion of cells as a group. As opposed to single cell migration, these collectively migrating cells retain the cell-cell adhesions among them. This type of cell migration is observed in a wide range of important physiological processes including tissue morphogenesis, wound healing and angiogenesis. In many developmental disorders, the underlying causes include genetic mutations that cause defective cell migration of cell groups in the embryo. During tumor metastasis, the faulty molecular machinery in tumor cells cause them to detach and migrate as a cluster, invading surrounding tissues. Thus, proper regulation of group cell movement is vital to maintain homeostasis of multicellular organisms. This study aims to understand the role of a biologically fundamental and highly conserved molecule, TOR (Target of Rapamycin) in collective cell migration using the border cell model system in Drosophila oogenesis. TOR (Target of Rapamycin) is an evolutionarily conserved kinase present in all eukaryotes. Its plays a pivotal role in many of the fundamental cellular and physiological processes. At the organism level, TOR regulates the development, metabolism, memory and aging. At the cellular level, TOR regulates the translation, transcription, metabolic processes and cytoskeletal rearrangement. These traditional roles of TOR and their mechanisms have been extensively investigated. TOR kinase is also known to regulate cell migration. However, this function is comparatively less characterized, in terms of the downstream targets and unclear molecular mechanisms. In this study, we report that TOR is essential for border cell migration. TOR depletion in border cell clusters led to their defective detachment and migration without affecting the specification of these cells. Moreover, the regulation of border cell migration by TOR is majorly through the TOR complex 1. While searching for downstream targets of TOR complex I that are mediating this function, REPTOR was found to affect border cell migration. Further experimental investigation confirmed that the REPTOR is one of the molecules downstream to TORC1 regulating border cell migration. Additionally, we report that TOR is required for the proper localization of Myosin II activity in border cell cluster.

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