Costagli, A.;
(2007)
Roles of reelin and disabled1 in neural development in zebrafish.
Doctoral thesis , University of London.
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Abstract
Reelin and Disabled 1 (Dabl) are known to be involved in neuronal migration in vertebrates and in particular in radial migration. Reelin is a secreted protein that can bind several receptors and the signal is intracellular transduced by Dabl. The final targets of the Reelin pathway are molecules that regulate cytoskeletal remodeling. In my project I studied the expression pattern of reelin and dabl in several areas of the zebrafish CNS. The differences found in the telencephalic expression of reelin and dabl between teleosts and tetrapods are likely to arise from the process of eversion, which is specific for the teleost telencephalon. On the contrary, all the other regions of the CNS present a conservative pattern of expression, in comparable structures among vertebrates, with the only exception of the olfactory bulb that does not express reelin in zebrafish. As the dabl gene shows a high degree of complexity in mammals and mice, I studied the genomic organization of the dabl gene in zebrafish and found a similarly complex organization. In order to study the functions of the Reelin pathway in neuronal migration in zebrafish, I performed loss of function experiments with morpholino antisense oligonucleotides. I found defects at level of several neuronal groups including the facial branchiomotor nucleus, the Mauthner neurons and neural crests. To investigate whether the role of dabl in the migration of these neuronal groups may be that of conveying a Reelin signal, I attempt to rescue these phenotypes by overexpressing full length dabl or truncated forms of the protein that lack the Reelin or the CDK5 responsive domains. It appears that the presence of the tyrosine domain, but not of the CDK5 phosphorylation domain, is necessary for partial resoiing of most of these phenotypes. I also found that some populations of neurons that express dabl show defects in neurites growth in morpholino injected embryos.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Roles of reelin and disabled1 in neural development in zebrafish. |
| Identifier: | PQ ETD:592718 |
| 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/1445398 |
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