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Publication Date

2022-05-09

First Advisor

Michael J. F. Barresi

Document Type

Honors Project

Degree Name

Bachelor of Arts

Department

Biological Sciences

Keywords

Zebrafish, behavior study, Reelin

Abstract

Reelin acts as a secreted extracellular glycoprotein that plays a role in neuronal migration and patterning during cortical development in the mammalian brain. Due to its essential role in neurogenesis in the embryo as well as synaptic plasticity in the adult, defects in Reelin signaling are linked to developmental, progressive, and psychiatric disorders, including, but not limited to, Autism Spectrum Disorder, Schizophrenia, and Alzheimer’s Disease. The Reelin ligand operates through two different receptors, Apolipoprotein E receptor 2 (ApoER2) and Very-Low-Density Lipoprotein receptor (Vldlr), which are known to mediate the cortical layering in the brain. How these receptors may differentially mediate Reeling signal transduction during CNS development and adult function remains unclear, however. We took advantage of the genetic tractability of the zebrafish model system to investigate how loss of reelin and its two receptors (apoER2and vldlr) affect social behavior in the adult zebrafish. We conducted three behavioral assays: a novel tank assay to examine exploratory behavior, a social preference assay to examine the ability to retain familiar connections, and a social novelty assay as a measure of anxiety tendencies. Currently, our analysis has focused on the apoer2 -/-, and preliminary results suggest the presence of novel sporadic behaviors with observed differences in both their social and exploratory behaviors. Using these zebrafish mutants we are systematically dissect the relative contributions Reelin and its two receptors play in the early embryonic construction of the CNS and how that translates into a pattern of adult fish behaviors. Using the aforementioned mutants and behavioral assays we found no significant behavioral differences when comparing them to their WT siblings. We also examined and compared the amount of time each fish spent moving versus during each assay and found that the mutants and their WT siblings they spent similar amounts of time moving and not moving. Due to the overall outcome showing no significant or distinct differences in behavior, we looked at the variable of sex. We found that the amount of time the apoer2 -/- males spent moving in comparison to their WT male counterparts showed some significance. To conclude, there are no overall behavioral phenotypes associated with the mutants; however, there is a behavioral phenotype in theapoer2 -/- males waiting to be explored in the future through doing more behavioral assays. Taking a closer look at apoer2 -/- males, in the future, will allow us to explore the interplay interplay between Reelin signaling, sex, and environmental differences on both embryogenesis and adult behavior. This research is supported by the Smith College Nancy Kershaw Tomlinson Memorial Fund.

Rights

©2022 Diamond Lewis. 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.

Language

English

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