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Title: Keep It Movin': Discovering motile ciliated cell types in the central nervous system
Authors: Davidson, Kerri
Advisors: Burdine, Rebecca
Department: Molecular Biology
Certificate Program: Global Health and Health Policy Program
Class Year: 2019
Abstract: Non-communicable diseases are the leading cause of early death and disability worldwide. Among these diseases, idiopathic scoliosis affects approximately 4% of the world’s seemingly healthy children. Additionally, the burden of patient care is significant; hospital stays for a child affected with scoliosis costs five times more than the average hospital stay. Despite these considerations, we have seen a decrease in school screening for the disease and a lack of biological and epidemiological research regarding the condition. Consequently, we know very little about the etiology of the disease, let alone a possible cure. Animal models can help advance our understanding of disease, and the Burdine lab previously used zebrafish to demonstrate an association between cilia motility and spinal curvature in a model of idiopathic scoliosis. I took advantage of the external development, transparency and genetic tractability of zebrafish to probe the heterogeneity of cells expressing motile cilia at juvenile stages. Single cell RNA sequencing of cells with motile cilia, followed by clustering analysis, revealed a large population of radial glial and neural progenitor cells. Notably, there was an absence of cells expressing ependymal markers. This suggests that either a technical issue prevented our identification of this cell type, or that ependymal cells are not the prime motile ciliated cells lining the brain ventricles and spinal canal at this stage. The second goal of my project was to generate zebrafish mutant for the idiopathic scoliosis candidate gene POC5, which has common single nucleotide variations among affected individuals, using vii CRISPR/Cas9 strategies. We were able to generate a POC5 mutant zebrafish with a truncation in the protein that led to scoliotic-like curvature. My studies therefore advance our understanding regarding the motile ciliated cellular composition of the central nervous system. Furthermore, we generate more zebrafish with defective cilia to further elucidate the role of cilia in maintain spine linearity. Overall, I have laid the ground work for continuing studies on the etiology of idiopathic scoliosis, which is necessary for the ultimate transfer of research achievements to therapeutic treatment development and clinical practices.
Type of Material: Princeton University Senior Theses
Language: en
Appears in Collections:Molecular Biology, 1954-2022
Global Health and Health Policy Program, 2017-2022

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