Pharmacological Effects on F-Actin Dynamics, A Study of Neural Development and Motor Function

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological and Environmental Sciences

Date of Award

8-14-2024

Abstract

Studying the effect of cytoskeletal dynamics on neural development should provide key understanding towards basic science as well as disorders and pathologies. Many disorders affecting motor development and abilities have been reported to be due to irregularities in actin dynamics caused by mutations in the protein itself or in interacting proteins. Therefore, this study hypothesizes pharmacological manipulations to actin dynamics will result in changes in motor function. For this, Latrunculin A, an actin destabilizer drug, and Jasplakinolide, an actin stabilizer drug, were utilized to manipulate the cytoskeletal dynamics of the wildtype Drosophila melanogaster (fruit flies) in the embryonic stage. The delivery method of drugs has been developed through a collection of research methods from literature and multiple trials of differing drug delivery protocols of embryo permeabilization. Embryo permeabilization techniques rely on removing the chorion and permeabilizing the vitelline membrane of embryos, allowing the pharmaceutical drugs to penetrate the embryo. In later developmental stages, established behavioral paradigms of larval crawling and adult geotaxis were exercised to assess and draw conclusions about changes in the animals’ locomotor abilities as a proxy to the state of the neuromuscular system. Larval crawling assays showed significant slowing in drug-treated animals compared to controls indicating perturbations to motor function whether actin structures were stabilized or destabilized in embryonic stage. However, adult geotaxis (RING) assays did not indicate significant changes in drug-treated animals compared to controls. This might indicate recovery mechanisms for cytoskeletal and neuromuscular systems throughout Drosophila’s life cycle. This study poses further questions about the effects of actin dynamics at the cellular level throughout development, and whether the neuron, muscle, or both are affected when treated with actin binding drugs.

Advisor

Hunkar Yesilyurt

Subject Categories

Medical Sciences | Medicine and Health Sciences | Neurosciences

Link to Full Text

Share

COinS