Orofacial anomalies make up about a third of the 120,000 birth defects each year in the United States. Children born with these abnormalities must undergo immense physical and emotional strain in order to correct the defects. In fact, about $697 million is spent every year surgically treating children with cleft lip and/or cleft palate (2011). In countries where surgery is not an option, this abnormality causes immense difficulties in eating, hearing, speech, and psychosocial development. The causes of cleft lip/palate are extremely complex. Genetics play a role in the anomaly; however, 95% of cleft palate cases are non-syndromic and likely due to other factors. Vitamin deficiencies, lack of folic acid intake during pregnancy, exposure to cigarette smoke, anticonvulsant drugs, alcohol, and inappropriate amounts of retinoic acid have all been correlated to incidence of cleft palate and other orofacial defects (Weingartner, Lotz et al. 2007). Xenopus laevis, and the closely related Xenopus tropicalis, are excellent model systems for orofacial development studies. The ease of embryo collection and manipulation, in addition to the conservation of DNA sequence between the two species, makes them ideal for studying developmental processes. Further, tissue specific experiments are extremely feasible due to the size of Xenopus oocytes (approximately 1000 times larger than a human egg!), and their ability to develop outside of the mother (Lindeman, Winata et al. 2010; Liu 2011). Here, I show that molecules from both the folic acid and retinoic acid pathways are highly expressed in the developing face. I have found that inhibition of key enzymes that regulate these pathways induces similar orofacial malformations, including median clefts that extend into the developing palate. Further, disruption of these pathways induces severe abnormalities in the formation of the cartilages of the jaws and face. Thus, both folic acid and retinoic acid are key signaling molecules that regulate proper formation of the orofacial region.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-1410 |
| Date | 21 June 2012 |
| Creators | Kennedy, Allyson |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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