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Title: The role of differential receptor signalling in the regulation of stem cell differentiation
Author: Boyle, J. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2009
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Stem cells have clinically relevant potential, as a source of tissue for cell transplantation therapies for the treatment of neurodegenerative disorders such as Parkinson’s disease and multiple sclerosis. In the first part of this thesis I focus on the role of the extracellular matrix molecule heparin in epidermal growth factor (EGF) signalling through the EGF receptor (EGFR) family of receptor tyrosine kinases (RTKs), concentrating on EgfR1 and ErbB4. I investigate its influence on receptor activation, cell proliferation and cell fate determination in mouse striatal neural stem cells (NSCs) and show that it can increase EGF signalling through both EgfR1 and ErbB4. I go on to examine how EGF signalling through ErbB4 may influence the cell fate specification of NSCs and, using micro array analysis, I investigate the influence of EGF on ErbB4 signalling on a molecular level. In the second part of this thesis I investigate the role of differential signalling through the retinoic acid nuclear receptors on the development of mammalian ventral midbrain dopaminergic neurons. Using retinoic acid receptor (RAR) subtype specific agonists I show that differential activation of the three RARs –alpha, beta and gamma- can influence human embryonic stem cell (hES cell) neutralisation and dopaminergic (DA) neuron specification. Finally, I show that RA or RAR agonist treated hES cells transplanted into neonate rats can survive in vivo for up to 12 weeks and differentiate giving rise to surviving DA neurons.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available