Show simple item record

dc.contributor.authorCameron, Donald
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2010-07-08 13:48:24.258en
dc.date.accessioned2015-07-29T16:10:34Z
dc.date.available2015-07-29T16:10:34Z
dc.date.issued2015-07-29
dc.identifier.urihttp://hdl.handle.net/1974/13461
dc.descriptionThesis (Ph.D, Biochemistry) -- Queen's University, 2010-07-08 13:48:24.258en
dc.description.abstractThe Hedgehog (Hh) family of secreted signalling factors play diverse roles in animal development. In mammals, the Hh ortholog Sonic hedgehog (Shh) is critical for the proper formation of the limbs, central nervous system, and axial skeleton, amoung other tissues. Mutations affecting the function of this pathway during development have severe consequences to the developing embryo and can cause birth defects in humans. Inappropriate activation of the pathway in adult tissues has also been implicated in several human cancers. In recent years several unexpected regulatory factors of the pathway during embryogenesis and in the adult have emerged through genetic studies in the mouse, such as proteins involved in vesicle transport and in the formation and function of primary (non-motile) cilia. Evidence is presented here that the mouse Tubby gene family member Tubby-like protein 3 (Tulp3) plays an important negative regulatory function in the Hh signalling pathway during embryogenesis, a role not previously associated with the Tubby proteins. Embryos lacking Tulp3 develop severe neural tube defects and polydactyly, along with ectopic activation of Shh target genes in the developing limbs and CNS, and altered Shh mediated axon guidance in the developing spinal cord. Moreover, Tulp3 was found to act largely independently of Shh, as compound Tulp3/Shh mutant embryos retain expression of Shh target genes and related abnormalities. Finally, the Tulp3 protein was found to localize to the primary cilium in cultured cells, implicating Tulp3, and possibly other Tubby proteins as regulators of cilium based signalling. These results have important implications in the understanding of the regulation of the Hh pathway, and in the emergence of Hh related birth defects and tumourigenesis.en
dc.languageenen
dc.language.isoenen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectHedgehog signallingen
dc.subjectEmbryonic developmenten
dc.subjectCongenital malformationsen
dc.subjectMouse geneticsen
dc.titleIdentification of TULP3 as a negative regulator of Hedgehog signalling in the mouseen
dc.typethesisen
dc.description.degreePh.Den
dc.contributor.supervisorPetkovich, Martinen
dc.contributor.departmentBiochemistryen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record