Abstract
The early developing thalamus forms two domains – a large caudal region (C-Th) and smaller rostral region (R-Th). C-Th neurons have been the focus of much research and develop a population of relay neurons that project to the cortex. The RTh, which has received far less attention, abuts the ZLI (zona limitans intrathalamica) at the rostral pole of the thalamus and is a novel source of GABAergic neurons within the Th. This region is the focus of this thesis.The data presented in this thesis show that the R-Th forms a highly motile and diverse population of cells. All the progeny from this region express the transcription factor Sox14. Using time lapse analysis on diencephalic tissue explanted from Sox14:GFP reporter mouse embryos at E11.5 to E14.5, I show that postmitotic R-Th neurons migrate tangentially both rostrally and caudally in a highly organised fashion. Knockout of Sox14 shows that this factor is essential for this migration.
I show that Sox14+/GABA+ neurons populate exclusively the nuclei of the subcortical visual shell (SVS) – the intergeniculate leaflet (IGL) lateral habenular (LHa), nucleus posterior limitans (PLi), and the ventral lateral geniculate nucleus (vLGN). These nuclei are all targets of non-image forming, melanopsin-expressing retinal ganglion cells (ipRGCs), which are involved in luminance detection, including entrainment of the circadian rhythm to light. These findings demonstrate that Sox14 is useful and reliable marker for the ontogeny of the SVS. Knockout of Sox14 leads to interesting luminance-detection phenotypes, involving circadian entrainment and negative masking of movement.
A further topic in this thesis is an investigation of molecular factors involved in tangential neuronal migration. A transcriptome analysis of Sox14+ positive regions has identified a number of candidate genes.
| Date of Award | 1 Jul 2019 |
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| Original language | English |
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| Supervisor | Andrew Lumsden (Supervisor) & Ivo Lieberam (Supervisor) |