The development of the zebrafish ear and a quest for genes involved in sensory patterning (pattern formation, Danio rerio)

In this thesis I have studied the ear of the zebrafish, Danio rerio during the first week of life. I have described the changing morphology of the ear, as it converts from a simple epithelial placode to a complex labyrinth, created a fate map for the early ear, observed the delamination of its neurons, and made an analysis of the spatial location and organisation of differentiated cells, with particular reference to the sensory regions of the epithelium. In these regions, mechanosensory hair cells are interspersed among supporting cells in a regular manner, leading to the suggestion that production of these cell types is controlled by lateral inhibition: each nascent hair cell might inhibit neighbouring cells from differentiating as hair cells, forcing them to become supporting cells instead. Analogies with Drosophila mechanosensory bristle development suggest that this lateral inhibition might be mediated by a Delta-Notch signalling mechanism. In order to test whether this could be the case in the zebrafish ear, I have cloned four zebrafish delta genes and examined their expression patterns along with a zebrafish notch gene, in the ear and elsewhere. In the wild type fish ear, the spatial and temporal expression patterns of these genes make them good candidates for a role in lateral inhibition-mediated control of hair-cell/supporting-cell differentiation. In the ear of the neurogenic mutant, $mindbombsp{wit},$ (which produces an excess of early-born CNS neurons as well as displaying several other defects, suggestive of a failure of Delta-Notch signalling), sensory hair cells are produced in excessive numbers at the expense of supporting cells; the levels of expression of deltaA, B and D are all increased at the sites where hair cells are about to differentiate. These findings encourage the view that the pattern of cell types in the ear's sensory patches is indeed controlled by a Delta-Notch mediated lateral inhibition mechanism, and that the reception of the inhibitory signal is defective in the $mindbombsp{wit}$ mutant. Elsewhere in the fish, delta genes are expressed in many other sensory sites, suggesting roles in neurogenesis, somitogenesis, lateral line and neuromast formation.