Molecular genetics of the imprinted gene - SPROUTY3 (SPRY3)

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dc.contributor.advisor Moore, Thomas F. en
dc.contributor.author Ning, Zhenfei
dc.date.accessioned 2015-06-09T09:17:18Z
dc.date.issued 2014
dc.date.submitted 2014
dc.identifier.citation Ning, Z. 2014. Molecular genetics of the imprinted gene - SPROUTY3 (SPRY3). PhD Thesis, University College Cork. en
dc.identifier.uri http://hdl.handle.net/10468/1845
dc.description.abstract Sprouty proteins are key regulators of cell growth and branching morphogenesis during development. Human SPRY3 which maps to the pseudoautosomal region 2, undergoes random X-inactivation in females and preferential Y-inactivation in males, behaving as though genetically X-linked. Spry3 is widely expressed in neuronal tissues, being found at high levels in the cerebellum and particularly in the Purkinje cells which, notably, are deficient in the autistic brain. Spry3 is also highly expressed in other ganglia in adults including retinal ganglion cells, dorsal root ganglion and superior cervical ganglion. SPRY3 enhancer can drive SPRY3 expression in the lung airway, which is consistent with a role in branching morphogenesis and the function of the original Drosophila Spry gene, which is critical for lung morphogenesis, providing a possible explanation for an observed anatomic abnormality in the autistic lung airway. In the human and mouse, the SPRY3 core promoter contains an AG-rich repeat and we found evidence of coexpression, promoter binding and regulation of SPRY3 expression by transcription factors EGR1, ZNF263 and PAX6. Spry3 over-expression in mouse superior cervical ganglion cells inhibits axon branching and Spry3 knockdown in those cells increases axon branching, consistent with known functions of other Sprouty proteins. Novel SPRY3 upstream transcripts that I characterised originate from three start sites in the X-linked F8A3 – TMLHE gene region, which is recently implicated in autism causation. Arising from these findings, I propose that the lung airway abnormality and low levels of blood carnitine found in autism suggest that deregulation of SPRY3 may underpin a subset of autism cases. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2013, Zhenfei Ning. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/ en
dc.subject SPROUTY3 en
dc.subject Autistic spectrum disorder en
dc.title Molecular genetics of the imprinted gene - SPROUTY3 (SPRY3) en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text not available en
dc.check.info Indefinite en
dc.check.date 10000-01-01
dc.description.version Accepted Version
dc.description.status Not peer reviewed en
dc.internal.school Biochemistry en
dc.internal.school Biosciences Institute en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out Yes en
dc.thesis.opt-out true
dc.check.entireThesis Entire Thesis Restricted
dc.check.embargoformat Both hard copy thesis and e-thesis en
dc.internal.conferring Summer Conferring 2014 en


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© 2013, Zhenfei Ning. Except where otherwise noted, this item's license is described as © 2013, Zhenfei Ning.
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