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dc.contributor.authorMacchiarulo, Stephania
dc.identifier.citationSource: Dissertation Abstracts International, Volume: 78-04(E), Section: B.;Advisors: Bernice E. Morrow.
dc.description.abstractTbx1 encodes a T-box transcription factor whose haploinsufficiency is responsible for many of the anomalies seen in the human congenital disorder, 22g11.2 deletion syndrome (22g11.2DS). Jag1 encodes a ligand whose haploinsufficiency causes the human congenital disorder Alagille syndrome. Individuals affected by these syndromes, independently, share a range of phenotypes including hearing loss and congenital heart disease. Here, for the first time, we demonstrate a biological connection between these two genes in multiple tissues during embryogenesis. We also provide a rationale for further investigation into a potential link between 22g11.2DS and JAG1.;The first part of this thesis demonstrates that concomitant loss of Jag1 and Tbx1 enhances a switch in the fate of cells within the early developing mouse otic vesicle from non-neurogenic to neurogenic. We suggest that alterations in Notch signaling contribute to this phenotype. We also show that Tbx1 acts at the neurosensory domain border in the otic vesicle to restrict cells expressing Jag1 and Sox2. In the second part of the thesis, we demonstrate that conditional homozygous inactivation of Jag1 with Tbx1cre resulted in cranioafacial anomalies, isolated pharyngeal arch artery anomalies, as well as defects in the thymus, parathyroid, and thyroid glands, partially recapitulating congenital anomalies seen in patients with 22g11.2DS. We suggest that Jag1 is required mainly within the pharyngeal epithelia (ectoderm and pouch endoderm), where it overlaps with Tbx1 expression, for the development of these structures. Finally, in the last part of this thesis, we show that Tbx1 is required autonomously in the core mesoderm of the pharyngeal arches, upstream of key myogenic genes, for core mesoderm cell survival needed for the formation of the muscles of mastication.
dc.publisherProQuest Dissertations & Theses
dc.subjectDevelopmental biology.
dc.titleInvestigation into the roles of Tbx1 and Jag1 in mouse embryogenesis

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