Honors Program Theses

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Open Access Honors Program Thesis

First Advisor

Darrell Wiens

Abstract

In the chick embryo, homocysteine (Hcys) is teratogenic at elevated levels, causing neural tube defects and cardiac malformations. There is evidence for several Hcys mechanisms of action, including inhibition of cyclin A and cdk2 in the cell cycle, increasing cytosolic calcium levels, and acting as a calcium chelator within adhesion molecules. Elevated Hcys also promotes detachment of endothelial cells, increases migration and proliferation of trunk neural crest cells, and acts as an antagonist to the NMDA receptor that mediates sympathetic pathways to the cardiovascular system. Elevated Hcys' effects on the cell cycle, intracellular and blood calcium levels, and cell proliferation and migration provide evidence that it may alter early heart development, which relies on these processes. By responding to FGF and BMP signals and inhibition of the Wnt pathway, the precardiac mesoderm rapidly differentiates into contracting heart tissue. ß-catenin, a transcription factor involved in the Wnt pathway, signals proliferation of precardiac mesoderm cells and development of heart cushion tissue. We tested the precardiac mesoderm's ability to develop contractions and its expression of ß-catenin when cultured in elevated levels of Hcys. Our results indicate that an elevated level of Hcys inhibits the contraction of cardiac tissue after incubation of precardiac mesoderm-endoderm explants in vitro. We also developed a color-threshold procedure to measure the area of antibody immunostaining at or above a set intensity level.

Year of Submission

2009

Department

Department of Biology

University Honors Designation

A thesis submitted in partial fulfillment of the requirements for the designation University Honors

Comments

If you are the rightful copyright holder of this thesis and wish to have it removed from the Open Access Collection, please submit a request to scholarworks@uni.edu and include clear identification of the work, preferably with URL.

Date Original

5-2009

Object Description

1 PDF file (v, 26 pages)

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