To access this work you must either be on the Smith College campus OR have valid Smith login credentials.
On Campus users: To access this work if you are on campus please Select the Download button.
Off Campus users: To access this work from off campus, please select the Off-Campus button and enter your Smith username and password when prompted.
Non-Smith users: You may request this item through Interlibrary Loan at your own library.
Reelin in autism spectrum disorders : an investigation of reelin-disabled signaling in zebrafish neurogenesis and disease
Reelin-disabled signaling in zebrafish neurogenesis and disease
Michael J.F. Barresi
Bachelor of Arts
Developmental biology, Zebrafish, Neurodevelopment, Autism spectrum disorders, Disease modeling, Reelin, Spinal cord, CRISPR-Cas9, Zebra danio-Development, Neurobiology, Diseases-Animal models, Mutagenesis
Disease can often be thought of as a fundamental breakdown of developmental processes. Based on this thinking, our understanding of pathology can be directly informed by our comprehension of the mechanisms that first constructed the tissues of the embryo. Understanding the way that our brains are built, from stem cells to neurons to glia, is an immensely complex and substantial task. It will be through the comprehension of the minute processes that occur in our developing brains, that we will be able to solve the complex problems that plague one of our most dynamic organs. Autism spectrum disorders, a complex neurodevelopmental disorder, is a perfect example of a condition that will only ever be understood through the precise analysis of the development processes that underlie its creation. Autism is a particularly challenging spectrum of disorders to understand, as its symptoms range from direct alterations in brain morphogenesis, to behavioral and social impairments. Defects in Reelin-Disabled signaling has been strongly associated with humans with autism spectrum disorders (Perciso et al., 2001). To better understand the role of Reelin signaling during embryonic brain development and disease, we are taking advantage of the zebrafish model for its unique combination of transparent, rapid, and extrauterine development paired with tractable genetic methods. Through CRISPR-Ca9 mediated mutagenesis, we generated nonsense mutations in reelin which yielded a viable, null-mutant. This is supported by the complete loss of Reelin protein expression, analyzed by immunohistochemistry. In addition to characterizing the mRNA expression of reelin, vldlr, apoer2 and dab1a/b, in the zebrafish spinal cord, we also began to characterize the migration of Islet1+ cells in the hindbrain and spinal cord of reelin mutants. Through the quantification of the position of Islet1+ cells, statistically significant differences in the dorsoventral positioning was observed in the junctional region, as well as difference in the mediolateral positioning in the ventral spinal cord, the mid junctional region and the ventral hindbrain. Furthermore, analysis of the locomotor behavior of reelin mutants showed a decrease in average waking activity as compared to wildtype. Further analysis of specific cellular and behavioral defects in the reelin mutant will allow further insights to be grained into the function of Reelin during normal development, and more significantly its role in autism spectrum disorders.
2018 Katrina G. Anderson. Access limited to the Smith College community and other researchers while on campus. Smith College community members also may access from off-campus using a Smith College log-in. Other off-campus researchers may request a copy through Interlibrary Loan for personal use.
Anderson, Katrina G., "Reelin in autism spectrum disorders : an investigation of reelin-disabled signaling in zebrafish neurogenesis and disease" (2018). Honors Project, Smith College, Northampton, MA.
Off Campus Download
49 pages : color illustrations. Includes bibliographical references (pages 46-49)