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dc.contributor.advisorNazarali, Adil J.en_US
dc.creatorSmith, Tara Marieen_US
dc.date.accessioned2009-09-14T18:36:53Zen_US
dc.date.accessioned2013-01-04T04:58:21Z
dc.date.available2010-09-22T08:00:00Zen_US
dc.date.available2013-01-04T04:58:21Z
dc.date.created2009-09en_US
dc.date.issued2009-09en_US
dc.date.submittedSeptember 2009en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-09142009-183653en_US
dc.description.abstractHoxa2 null embryos display a high incidence of cleft secondary palate which has previously been described as secondary to altered tongue development. The experiments described in this thesis demonstrate that expression of Hoxa2 does occur within the developing palate, with the highest levels appearing in the early stages of palatogenesis (E12.5 and E13.5). Increased cell proliferation was observed throughout the palate in the absence of Hoxa2, without a detectable difference in apoptosis or the ability of the shelves to fuse. In addition, the palate shelves of the null embryos failed to elevate above the tongue, suggesting a mechanism by which the increased cell proliferation results in cleft palate. Numerous downstream targets of Hoxa2 were also identified in the palate (Msx1, Bmp4, Barx1, Ptx1, Six2, Lef1 and Tbx1). In all cases, Hoxa2 appears to act as a transcriptional repressor. Increases in palatal Msx1, Bmp4 and Barx1 expression have all been previously described to lead to increases in cell proliferation. Hoxa2, Ptx1, Lef1 and Tbx1 may be involved in a novel pathway that regulates proliferation in the palate. In addition, three novel gene targets were identified in the palate, Six2, Fgf8 and Htra3. Together these data show that there is a direct role for Hoxa2 in regulating palate development, apparently through regulating the expression of downstream genes involved in maintaining normal cell proliferation rates.en_US
dc.language.isoen_USen_US
dc.subjectSix2en_US
dc.subjectBmp4en_US
dc.subjectMsx1en_US
dc.subjectPtx1en_US
dc.subjectproliferationen_US
dc.subjectHox genesen_US
dc.subjectsecondary palate developmenten_US
dc.titleThe role of Hoxa2 and characterization of its new downstream targets in murine palatogenesisen_US
thesis.degree.departmentCollege of Pharmacy and Nutritionen_US
thesis.degree.disciplineCollege of Pharmacy and Nutritionen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberDobson, Royen_US
dc.contributor.committeeMemberLozanoff, Scotten_US
dc.contributor.committeeMemberPaterson, Phyllisen_US
dc.contributor.committeeMemberSingh, Baljiten_US
dc.contributor.committeeMemberKulyk, Williamen_US


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