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Title: Development of monoaminergic systems : morphogenetic roles and early specification
Author: Vitalis, Tania
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Serotonin is often regarded as a powerful morphogen, however proofs of its action are often missing. In my thesis, I demonstrated that a transient excess of serotonin created pharmacologically by inhibition of the MAOA enzyme altered the formation of barrels of both thalamocortical axons and granular neurons in the layer IV of the developing somatosensory cortex. Thalamocortical axon alterations are characterised by a state of exuberance. A small family of molecules, neurotrophins, has been shown to control early events in the developing thalamus and cortex such as cell survival, neurite outgrowth, migration, or dendritic and axonal morphologies. I showed that trkB, an essential neurotrophin receptor, was expressed in the cortex during the critical period of serotonin sensitivity. Analysis of mice lacking trkB showed subtle alterations in the thalamocortical projections, suggesting that trkB is not essential in the establishment of the barrel field. By obtaining mice lacking MAOA and trkB, I showed a synergistically altered phenotype in the thalamocortical projection, suggesting that in normal conditions serotonin and trkB signalling act synergically in the refinement of the somatosensory thalamocortical map. I also studied the spatio-temporal pattern of MAOA and MAOB and showed striking features during early development: MAOA is tightly linked to the serotoninergic and catecholaminergic phenotypes and MAOB is tightly linked to the glial cell lineage. Analysis of mice lacking Pax6 showed that Pax6 was not essential to monoaminergic development but this study revealed that Netrin-1 was potentially important to the axonal pathfinding of dopaminergic neurons. Analysis of mice lacking Netrin-1 or it receptor deleted in colorectal cancer (DCC) confirmed that Netrin-1 is important but not essential for the axonal guidance of subsets of dopaminergic neurons. More interestingly, this study revealed that the interaction between Netrin-1 and DCC could be important for the cell survival of developing dopaminergic neurons.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available