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Effects of altered folate metabolism on specific gene expression in the developing Xenopus embryo

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Bupathi S. Dissanayake (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Karen Katula

Abstract: "Approximately 1 out of every 2000 births in the United States is affected by neural tube defects. The most well-known environmental cause of neural tube malformation is folate deficiency in pregnant women. The underlying mechanism for this relationship is unclear. The goal of this study was to determine if altered folate metabolism during early development leads to changes in the expression of selected genes. Xenopus laevis embryos were treated with different concentrations of homocysteine (0.5 mM, 1 mM, 10 mM, 25 mM , 50 mM and 100 mM) and methotrexate (1 uM, 10 uM, 50 uM, 100 uM and 200 uM) and their gross morphology, direction of gut coiling and neural tube thickness were analyzed. At higher concentrations both compounds caused morphological defects, including delayed development, kinked bodies, reduced body size and lack of gut structure. The percent of guts coiling to the left decreased from 93% to 5% as the homocysteine concentration increased from 0 mM to 10 mM. Meanwhile the guts coiling to the right increased from about 5% to 39%. The percent of guts deformed or mis-coiled increased from 5% to 100%, with the homocysteine concentration increasing from 0 mM to 50 mM. Methotrexate also affected the morphology and direction of gut coiling in a concentration dependent manner. The thickness of the dorsal side of the neural tube of the methotrexate treated embryos decreased from about 6 mm to 3 mm as the concentration increased from 0 uM - 200 uM. The effect of homocysteine on the neural tube thickness was less clear. Gross morphological effects and gut coiling suggest treatment of embryos with homocysteine and methotrexate affect embryos in a similar manner consistent with folate deficiency. In situ hybridization was performed on treated and untreated embryos to analyze changes in expression patterns of Dkk-1, Pax-3, Xbra, Xtwist and Wnt-5A genes. Gene expression patterns of Xbra and Xtwist were not affected by folate deficiency whereas Dkk-1 and Pax-3 expression appear to be down regulated. Wnt-5A data were inconclusive. These findings suggest that specific gene expression changes may be associated with folate deficiency. More studies are required to confirm these results."--Abstract from author supplied metadata.

Additional Information

Publication
Thesis
Language: English
Date: 2006
Keywords
births, United States, neural tube defects, folate, deficiency, pregnancy, metabolism, genes, Xenopus laevis, embryos, homocysteine
Subjects
Folic acid--Metabolism--Genetic aspects
Xenopus laevis