Degree
Doctor of Philosophy (PhD)
Department
Biological Sciences
Document Type
Dissertation
Abstract
The formation of three-dimensional tubes by invagination from flat epithelial sheets is a fundamental process in forming organs, such as lungs and kidneys. Defects in tube formation can lead to many diseases, such as spina bifida and pulmonary agenesis. Therefore, determining the mechanisms underlying tube formation is essential to understanding many developmental processes and common human diseases. To investigate the regulatory mechanisms behind the formation of epithelial tubes, the Chung lab uses Drosophila melanogaster as a model system with simple and complex epithelial tubular organs such as the salivary gland (SG) and trachea. My work broadly aims to identify and characterize the roles of the key components involved in Drosophila epithelial tube formation. Drosophila SG and tracheal invagination follows stereotypical cell shape changes regulated by molecular components of the cells. Yet, how the signaling at the cell surface is sensed and transduced downstream during epithelial tube formation remains obscure. In Chapters 2 and 3, I identified one ubiquitous and two tissue-specific GPCRs that regulate tube formation during Drosophila embryogenesis. Moreover, once the SG cells are specified, they do not die or divide until morphogenesis is completed. The molecular mechanisms underlying the regulation of cell cycle and patterning are yet to be discovered. In Chapter 4, I elucidate how defects in the cell cycle can affect morphogenesis during SG invagination. Filamins are highly conserved actin crosslinking proteins playing critical roles in development and diseases. Our knowledge of the roles of filamins in Drosophila is relatively limited. In Chapter 5 of this study, I reveal the roles of Jitterbug (Jbug) filamin during epithelial tube formation. We address our questions by applying fly genetics, immunohistochemistry, confocal microscopy, biochemical approaches, and computational image analysis. The findings from my work will fill the gap in our knowledge of the signaling pathway by revealing the roles of critical components that play a crucial part during epithelial tube formation. Overall, new knowledge from this study can be applied towards the formation of other tubular organs during development and help treat diseases due to defective tube formation.
Date
11-10-2023
Recommended Citation
Vishwakarma, Vishakha, "Regulatory mechanisms of epithelial tube formation during Drosophila embryogenesis" (2023). LSU Doctoral Dissertations. 6288.
https://repository.lsu.edu/gradschool_dissertations/6288
Committee Chair
SeYeon Chung