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dc.contributor.advisor Kirby, Margaret L en_US
dc.contributor.author Dyer, Laura Ann en_US
dc.date.accessioned 2009-08-27T18:39:32Z
dc.date.available 2011-08-27T04:30:07Z
dc.date.issued 2009 en_US
dc.identifier.uri http://hdl.handle.net/10161/1334
dc.description Dissertation en_US
dc.description.abstract <p>The two major contributing populations to the outflow tract of the heart are the secondary heart field and the cardiac neural crest. These two populations are responsible for providing the myocardium that supports the outflow tract valves, the smooth muscle that surrounds these valves and the outflow vessels themselves, and the septum that divides the primitive, single outflow tract into an aorta and pulmonary trunk. Because the morphogenesis of this region is so complex, its development is regulated by many different signaling pathways. One of these pathways is the Sonic hedgehog pathway. This thesis tests the hypothesis that Sonic hedgehog induces secondary heart field proliferation, which is necessary for normal outflow tract development. To address this hypothesis, I took advantage of small chemical antagonists and agonists to determine how too little or too much hedgehog signaling would affect the secondary heart field, both in in vitro explants and in vivo. I have determined that Sonic hedgehog signaling maintains proliferation in a subset of secondary heart field cells. This proliferation is essential for generating enough myocardium and smooth muscle and also for the cardiac neural crest to septate the outflow tract into two equal-sized vessels. Up-regulating hedgehog signaling induces proliferation, which is quickly down-regulated, showing that the embryo exhibits a great deal of plasticity. Together, these studies have shown that Sonic hedgehog promotes proliferation in a subset of the secondary heart field and that the level of proliferation must be tightly regulated in order to form a normal outflow tract.</p> en_US
dc.format.extent 49036095 bytes
dc.format.mimetype application/pdf
dc.language.iso en_US
dc.subject Biology, Cell en_US
dc.subject cardiac neural crest en_US
dc.subject DiGeorge syndrome en_US
dc.subject outflow tract en_US
dc.subject secondary heart field en_US
dc.subject Sonic hedgehog en_US
dc.title The Role of Sonic Hedgehog in Outflow Tract Development en_US
dc.type Dissertation en_US
dc.department Cell Biology en_US
duke.embargo.months 24 en_US

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