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dc.contributor.advisorLimpach, Aimee L.en_US
dc.contributor.authorMurari, Catherineen_US
dc.date.accessioned2010-03-23T15:56:47Z
dc.date.available2010-03-23T15:56:47Z
dc.date.issued2010-01en_US
dc.identifier.otherThesis-Murari-2010.pdf
dc.identifier.urihttp://hdl.handle.net/10504/5647
dc.description.abstractThe limb buds of the early embryo are formed at the lateral flank by an outgrowth of cells from a layer of embryonic tissue called the lateral plate mesoderm. Shortly after this initial outgrowth, cells from the lateral edges of adjacent developing tissue invade the limb bud to form the muscles, nerves and vessels of the limb. The limb bud increases in size and the individual skeletal elements are laid down along the body axis in an inner to outer fashion. Anteroposterior patterning of the developing limb is controlled by a small group of cells located along the postaxial limb bud border called the zone of polarizing activity (ZPA). The secreted molecule, sonic hedgehog (Shh) is produced by the cells of the ZPA and has been shown to play an important role in this process of pattern formation. Grafting the cells of the ZPA onto developing host tissue induces mirrorimage limb duplication. In addition to this, exposing embryos to exogenous Shh results in polydactyly. Polydactyly is a birth defect characterized by the presence of more than the normal number of fingers or toes. This defect with or without associated malformation(s) is found to be 5 to 19 in every 10000 births. To further understand the etiology of abnormal limb development, we have generated a mutant mouse line that mis-expresses Shh. Alcian blue staining of cartilaginous tissue shows that these mutant mice exhibit polydactyly and other related skeletal defects. Differences in gene expression between mutant and control mice were assessed using in-situ hybridization with probes for Fgf8, Fgf10 and Shh.|Taken together, morphological and molecular expression analysis data supports our hypothesis that mis-expression of Shh leads to digit duplication defects.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright Catherine Murarien_US
dc.subject.meshBody Patterning--geneticsen_US
dc.subject.meshGene Expression Regulation, Developmental.en_US
dc.subject.meshExtremities--embryologyen_US
dc.subject.meshHedgehog Proteinsen_US
dc.titleThe Misexpression of Sonic Hedgehog Leads to Digit Duplicationen_US
dc.typeThesis
dc.rights.holderCatherine Murarien_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.pagesvi, 57 pagesen_US
dc.contributor.cuauthorMurari, Catherineen_US
dc.degree.levelMS (Master of Science)en_US
dc.degree.disciplinePharmaceutical Science (graduate program)en_US
dc.degree.nameM.S. in Pharmaceutical Sciencesen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeShara, Michaelen_US
dc.degree.committeeSanchez, Sonia M.en_US
dc.degree.committeeKhan, Manzoor M.en_US


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