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Mechanisms of patterning and neurogenesis in the zebrafish forebrain

Shanmugalingam, Shantha Ganesh; (2000) Mechanisms of patterning and neurogenesis in the zebrafish forebrain. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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The vertebrate forebrain is a highly complex structure containing millions of neurons that form highly ordered and precise connections. The mechanisms that give rise to this complexity are slowly being elucidated through work on a number of developmental systems. I have investigated the organisation of the zebrafish forebrain and the mechanisms by which a simple neuroepithelial sheet becomes patterned to the more complex adult forebrain structure. Initially, I examined the development of the zebrafish CNS during later stages of development (18 somites stage to 5 days postfertilisation) through studies on gene expression, axon pathfinding, morphology and cell proliferation. Using the prosomeric model as a basis, we can begin to understand how the regions demarcated by genes, such as Dlx2 and Emx1, relate to similar regions in other organisms, such as mice, chickens and turtles. In order to investigate the how different genes influence forebrain development, I conducted misexpression studies and have characterised zebrafish mutants. Analysis of the acerebellar mutant reveals that Ace/Fgf8.1 is responsible for correct specification of, and axon pathfinding within, the midline optic stalk territory. Furthermore Ace/Fgf8.1 is also responsible for neuronal differentiation in the dorsal forebrain and for correct specification of the olfactory bulb. Analysis of zebrafish embryos with mutations in both Ace/Fgf8.1 and Syu/Shh reveals that although patterning of the forebrain is not more severely affected in the double mutant, the growth of the ventral forebrain is greatly reduced. In zebrafish, the members of the Emx gene family are the earliest known markers for the presumptive telencephalon and loss of function studies in Drosophila and mice suggest an important role for Emx genes in development of anterior structures. To further investigate potential roles for Emx genes in forebrain development, the zebrafish homologues of Emx genes were misexpressed. However ectopic expression of Emx genes does not appear to have the capacity to promote ectopic telencephalic structures. In conclusion, my study has started to reveal how the zebrafish forebrain develops and the genes involved in growth, patterning, neurogenesis and axon pathfinding in the forebrain.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Mechanisms of patterning and neurogenesis in the zebrafish forebrain
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
URI: https://discovery.ucl.ac.uk/id/eprint/10101314
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