Date of Award
2025
Degree Type
Thesis
Degree Name
Master of Science in Biological and Environmental Sciences (MSBES)
Specialization
Cell and Molecular Biology
Department
Biological Sciences
First Advisor
Niall G. Howlett
Abstract
Fanconi Anemia (FA) is a rare human genetic disease caused by mutation of any of twenty-three genes on the FA pathway, which functions in the repair of DNA damage and the maintenance of genome stability. FA is clinically characterized by congenital abnormalities and a predisposition to aplastic anemia and malignancies. Recently, progressive neurological symptoms and abnormal neurological findings on imaging have been noted in FA patients, including cerebral and cerebellar lesions, calcification, necrosis, gliosis, and associated acute and chronic neurological symptoms; this constellation of symptoms has been termed Fanconi Anemia-Associated Neurological Syndrome (FANS).
To elucidate the molecular etiology of FANS, our lab has turned to the model organism Caenorhabditis elegans. In this study, we have focused on the role of the C. elegans ortholog of human FANCI, fnc1-1, in nervous system development and function. We performed a series of behavioral assays with fnci-1 deletion strains under base-line conditions and conditions of replicative stress during neurogenesis. We have found that loss of fnci-1 results in broad developmental and functional neurological defects. To examine the effects of loss of fnci-1 on specific neuronal classes, we have generated crosses between mutant strains and strains with GFP-tagged neurons. Analyses of fnci-1-mutant animals after exposure to DNA-damaging agents have revealed significant differences in numbers of cholinergic, dopaminergic, glutamatergic, and GABAergic neurons compared to wildtype animals.
We anticipate that our work will help clarify the role of FANCI and the FA pathway in the development and maintenance of the central nervous system, with a view to discovering new therapeutic options for FANS patients.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Recommended Citation
Collins, Meagan, "INVESTIGATING THE ROLE OF FNCI-1 IN THE DEVELOPMENT AND FUNCTION OF THE C. ELEGANS NERVOUS SYSTEM" (2025). Open Access Master's Theses. Paper 2672.
https://digitalcommons.uri.edu/theses/2672