Characterisation of neurogenesis and neuronal subtypes in the embryonic zebrafish telencephalon.

The telencephalon is the embryonic structure that in mammals gives rise to the cerebral cortex and the basal ganglia. Despite the manifest differences in size, structure and function of telencephalic derivatives in different vertebrate species, the underlying patterning of the embryonic telencephalon is highly conserved. Very little is known about the development of the zebrafish telencephalon beyond the earliest embryonic stages of neural induction and patterning. One major outstanding question is the mechanism underlying telencephalic eversion, a process that is peculiar to ray-finned fish and that results in the dorsal telencephalon folding out laterally rather than evaginating as it does in most other vertebrate species. I used a range of techniques to monitor proliferation, neurogenesis, and axon extension over the entire period of embryogenesis. This led me to propose a mechanism for an observed rearrangement within the telencephalon between 2 and 3 days post fertilisation (dpf) that may also underlie the eversion process. To characterise the neuronal populations of the dorsal telencephalon I made a careful expression analysis of three LIM-homeobox (Lhx) genes, genes that are involved in neuronal subtype specification in a variety of systems. The Lhx genes lhx1a, lhx1b and lhx5 are expressed in spatially co-ordinated overlapping domains in the dorsal telencephalon and some of these genes are later expressed in the telencephalon-derived olfactory bulb. This suggested a dorsal origin of some olfactory bulb neurons. To further probe the morphogenetic movements and cell migrations that shape the zebrafish telencephalon I performed a fate map of the 1dpf telencephalon. I developed a cell labelling technique that uses the Kaede protein, a green fluorescent protein that is converted to a red fluorescent form on irradiation with UV light. By labelling small groups of cells in the 1dpf telencephalon and following them to their positions at 5dpf I established that the most posterior regions of the dorsal telencephalon contribute to the OB at 5dpf. In addition I identified two populations of migratory cells in the ventral telencephalon, contributing cells to the OB and the dorsal telencephalon respectively. These populations may reveal a previously unknown conservation between fish and tetrapods