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dc.contributor.authorCogger, Kathryn
dc.date.accessioned2013-01-11T14:37:49Z
dc.date.available2013-01-11T14:37:49Z
dc.date.issued2012
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/3167
dc.descriptionPhDen_US
dc.description.abstractPrimary cilia are sensory organelles found on most vertebrate cells during interphase. They play key roles in development, cell signalling and cancer, and are involved in signal transduction pathways such as Hh and Wnt signalling. The adrenal cortex produces steroid hormones essential for controlling homeostasis and mediating the stress response. Signalling pathways involved in the process of its development and differentiation are still being identified but include Hh and Wnt, and adrenal development is thus likely to require cilia. I have demonstrated that inhibiting cilia formation, using siRNA targeted to different ciliary components, results in reduced differentiation of the human adrenal carcinoma cell line H295R towards a zona glomerulosa (zG)-like phenotype. These data suggest that primary cilia play a key role in adrenal differentiation, but which signalling pathways are involved still remains unclear. I have also discovered that adrenals from Bardet-Biedl syndrome (BBS) mice, the most prominently studied ciliopathy, have thin capsules, the proposed adrenal stem cell niche, and abnormal histology, while zebrafish embryos injected with morpholinos targeting BBS genes show delayed and reduced expression of ff1b, a marker of interrenal tissue. These data further suggest a role for primary cilia in adrenal development and maintenance. These studies are the foundation for elucidating the role of primary cilia in the development and function of the adrenal gland, and furthering our understanding of adrenocortical development. This promises to lead to improved management of adrenal dysfunction, and demonstrating that adrenal defects are a characteristic of ciliopathies will potentially inform new strategies for patient care.en_US
dc.description.sponsorshipMedical Research Councilen_US
dc.language.isoenen_US
dc.subjectMedicineen_US
dc.titleThe role of primary cilia and sonic hedgehog signalling in adrenal development function.en_US
dc.typeThesisen_US
dc.rights.holderThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the author


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    Theses Awarded by Queen Mary University of London

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