Browsing by Subject "Genetics, Cell Biology, and Development"

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    Effects of Simultaneous Amyloid-Beta 42 and Heparan Sulfate Proteoglycan Expression on Alzheimer's Disease Incidence in Drosophila melanogaster Flies
    (2020) Roy, George; Ngoboka, Jessica; Nakato, Hiroshi
    Alzheimer’s disease is a serious neurological disorder that increases in severity with age. Previous research has correlated Alzheimer’s disease with the formation of amyloid-beta 42 (AB42) protein aggregates. Heparan Sulfate Proteoglycans (HSPGs) are a type of molecule known to interact with protein aggregates. Relatively little research exists studying the relationship between HSPGs and Alzheimer’s disease. Given this, the effects of HSPG overexpression and sulfation on Alzheimer’s disease formation in AB42-overexpressing Drosophila flies was investigated. Climbing assays were performed on Drosophila flies overexpressing AB42 and HSPG dally, and on Drosophila overexpressing AB42 and expressing non-sulfated HSPGs. Control group flies genetically identical to these groups with wild-type expression were also tested. Climbing assays were performed throughout the lives of Drosophila, with group average pass rates being recorded at each tested age. Ultimately, flies overexpressing HSPGs and AB42 experienced increased motor and cognitive degradation with age, whereas flies expressing un-sulfated HSPGs and AB42 experienced less degradation than controls. These results suggest that the interaction of HSPGs with AB42 may be significant to Alzheimer’s disease development in Drosophila and that this interaction may be dependent on the sulfated status of HSPG. However, experimental results were somewhat confounded by the absence of a Drosophila group dedicated to exclusively overexpressing AB42 in the absence of HSPGs.
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    Molecular Analysis of Pax3 in the Development of Neural Crest Cells
    (2012-04-18) Hoffman, Kirsta
    Neural crest cells, a transient population of cells that exists only during embryonic development, migrate from the neural tube to many different locations in the embryo where these cells are able to differentiate into a wide variety of terminal cell types, including cardiac cells, adipocytes, neurons, and melanocytes. Pax3 is one transcription factor known to play a role in the induction of neural crest development and the terminal differentiation of migrated neural crest cells. Pax3 also plays a role in skeletal muscle development, and in this lineage it has been shown to be a weak transcriptional activator and may require the binding of cofactors to increase its efficiency, but the only cofactors isolated to date are corepressors that reduce its activity. In order to study the cofactors of Pax3, we first began optimizing the culture conditions to efficiently generate neural crest cells from Pax3 mouse embryonic stem cells. Here we show that when comparing neural crest growth in an embryoid body system and a monolayer system, differentiating stem cells in a monolayer may be a better system for the generation of neural crest cells. While results are preliminary, they indicate that more experiments need to be performed to generate the optimum culture conditions. This would allow for further experiments aimed at isolating the cofactors of Pax3, which are imperative to identify in order to better understand the function of Pax3 in neural crest development and to better understand the processes and genes that govern the development of these cells.