|dc.description.abstract||Neural development is initiated by several signaling molecules including BMP-4, noggin, and chordin. These molecules induce the formation of neural plate, which later folds to become the spinal cord and part of the primitive brain. Because these signaling axes are sensitive to external factors, the process of neural development is subjected to an intense level of vulnerability. An environmental toxin, such as methoxychlor, can disrupt the molecular signaling axis during development An insecticide used as a replacement for DDT, methoxychlor was removed from the market due to its ability to contaminate drinking water, resulting in reproductive problems. Methoxychlor’s endocrine disrupting properties have warranted a closer look at its role, if any, in disrupting normal neural development.
Studies on transcription factors such as Sox2, which is responsible for maintaining neural stem cells in their pleuripotent state, have suggested that thyroid hormone has a significant role in the progression of neural development. A closer examination of genes containing thyroid hormone response elements can be utilized to gain an understanding of thyroid regulated gene expression.
We built a construct containing two DR4 thyroid response elements linked to a minimal SV40 promoter. This regulatory region drives luciferase expression, which we are able to measure in a laboratory reporter assay. The aim of this project is to determine, via a luciferase assay, the effect of methoxychlor exposure in thyroid hormone’s control of transcriptional activity during neural development.||