Semester of Graduation

Spring 2021

Degree

Master of Science (MS)

Department

Department of Biological Sciences

Document Type

Thesis

Abstract

Impairment of ribosome biogenesis disrupts cellular homeostasis and, in the process, causes a state of nucleolar stress in a cell. This triggers human syndromes collectively known as ribosomopathies. One such ribosomopathy is the Treacher Collins syndrome (TCS) which causes congenital craniofacial birth defects and hearing loss in patients. In TCS migration of neural crest cells during development is hindered by the loss of the ribosome assembly factor, treacle, and consequent apoptosis of these progenitor cells. Modeling this disorder in Drosophila was previously accomplished by disruption of Nopp140, treacle’s closest equivalent in Drosophila. During nucleolar stress, the Mushroom Body neuroblast population demonstrates resilience to the loss of Nopp140 with continued proliferation. These fruit flies also show an increase in total protein quantity of coilin, an integral component of the nuclear ribonucleoprotein assembly site, the Cajal body. We examined the variation of affected cell populations in TCS and other ribosomopathies by looking coilin expression at the neuroblasts with and without Nopp140. Neuroblasts in wild type brains already showed higher coilin levels relative to neurons. Coilin also showed a substantial distribution across the nucleoplasm of neuroblasts instead of appearing in bright Cajal body foci. In the absence of Nopp140, the Mushroom Body neuroblasts had increased coilin levels compared to other neuroblasts and neurons. We suspect that coilin plays a role not only in the selective resilience of Mushroom Body neuroblasts but also in cellular nucleolar response pathways.

Committee Chair

DiMario, Patrick J.

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