Hawkins, T.;
(2004)
The control of central nervous system myelination and the phenotypic characterisation of a novel zebrafish mutant: akineto(u45).
Doctoral thesis , University of London.
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Abstract
Part 1 of this thesis addresses the control of myelination in the central nervous system (CNS). We have a sound knowledge of myelin structure, particularly the molecules and cells involved in its make-up. However, our understanding of the control of myelin formation is scanty. Myelination of CNS tracts during development follows a strictly ordered schedule suggesting local control by axons. Here I present evidence that CNS axons need to form synaptic connections before they can be myelinated. I have used myelin renewal during regeneration of the fish optic nerve as a model system: the axons withstand target deprivation and their behaviour in these circumstances is well characterised from earlier studies of synaptic plasticity. Depriving the regenerating optic nerve of its primary target, the contralateral optic tectum, delays myelination until the regenerating axons find the intact ipsilateral tectum and form synapses there. Facilitating this process hastens the onset of myelination and denying the axons of any opportunity to form synapses abolishes it. I investigated possible mechanisms by which the synaptogenesis-timed signal is mediated and also compared myelination during regeneration and development. Part 2 describes the phenotypic characterisation of a novel zebrafish mutant: akineto (aknu45). Aknu45 mutant embryos cannot contract their skeletal muscles. Here I show that this is caused by incomplete sarcomere assembly. Myofibrils of mutants lack properly assembled thick filaments. Our understanding of the process of myofibrillogenesis, particularly relating to thick filament assembly, is mostly speculative at present. Although the aknu45 gene is unidentified so far, I am currently engaged in efforts to identify it. Subsequently the aknu45 mutation may become a useful tool to further unravel the process of myofibrillogenesis.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | The control of central nervous system myelination and the phenotypic characterisation of a novel zebrafish mutant: akineto(u45). |
| Identifier: | PQ ETD:602641 |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Thesis digitised by Proquest |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1446716 |
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