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Title: Development of the mesencephalic trigeminal nucleus in the zebrafish
Author: Dyer, Carlene
Awarding Body: King's College London (University of London)
Current Institution: King's College London (University of London)
Date of Award: 2011
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The mesencephalic trigeminal nucleus (MTN) forms part of the monosynaptic trigeminal circuit and is essential for eating and suckling in mammals. Little is known about how the MTN forms. For this thesis I aimed to elucidate the molecular and cellular basis of MTN development. I also aimed to investigate the role of the Fgf and Wnt signalling pathways in MTN development. The zebrafish was used as a model organism to investigate these aims. Putative MTN cells in zebrafish larvae were retrogradely labelled by applying Dil to the adductor mandibulae, a jaw closing muscle. Labelled axons projected from muscles via the trigeminal ganglion to cell bodies in the dorsal anterior mesencephalon, suggesting that the MTN does innervate jaw muscles in teleosts, contrary to previous studies. Molecular characterisation of the MTN in zebrafish revealed a similar expression profile as the mammalian MTN. To investigate whether MTN neurons are neural crest-derived, the neural crest was ablated, which resulted in an increase in MTN number. This suggests that the neural crest may play an inhibitory role in MTN development contradictory to previous studies in chick that suggested MTN neurons are derived from the neural crest. The role of the Fgf and Wnt signalling pathways was investigated by analysis of mutants and drug treatments where the pathways had been genetically or chemically manipulated. Down-regulation of Fgf signalling showed an increase in MTN neuron numbers, suggesting that Fgf signalling from the midbrain/hindbrain boundary inhibits development of the MTN in the midbrain. When the Wnt pathway was up-regulated there was also an increase in MTN neuron number. Based on the results from these experiments a model is proposed, in which Fgf signalling regulates the formation of MTN neurons in a spatial and temporal manner, and Wnt signals from the dorsal roof plate induce the proliferation of MTN precursor cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available