Bostock, Matthew Paul; (2022) Investigating the roles of Hedgehog signalling in the developing lamina of the Drosophila melanogaster visual system. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Neurodevelopment is controlled by complex and tightly controlled mechanisms. They function to ensure neuronal diversity at the right time and location. These processes can be activated non-autonomously when surrounding cells release biochemical signals, for example, Hedgehog (Hh) in Drosophila melanogaster. Hh signalling is frequently required during neurodevelopment where it regulates cell specification and numbers. The Drosophila melanogaster visual system is comprised of the retina and the optic lobe, which is further divided into four processing layers: lamina, medulla, lobula and lobula plate. During the development of the visual system, Hh signalling induces photoreceptor differentiation in the eye disc (developing retina). Consequently, photoreceptors transmit Hh to the optic lobe to the outer proliferation centre neuroepithelium. Photoreceptor-derived Hh induces lamina precursor cell (LPC) specification, terminal divisions and characteristic lamina column formation. My thesis re-examined the role of Hh signalling in early lamina development (prior to and up to column formation) and late lamina development (after column assembly). Overall, I discovered multiple instances where LPCs developed independently of Hh signalling, where the only intervention was blocking cell death. Secondly, I investigated which signal could be required to specify LPC fate. I found that blocking the expression of Aop, a transcriptional repressor as part of the MAPK cascade, blocked lamina development. Finally, I investigated how lamina neuron specification is controlled during late lamina development. Inducing high and low levels of Hh signalling activity gives rise to different lamina neuron fates. Furthermore, I found that Hh protein was distributed in a gradient. This work is exciting since the precise mechanisms that go into gradient formation are yet to be understood fully. It has been reported that Hh signalling is disrupted in several rat models of neurodegeneration. My findings implicate the genetically tractable Drosophila melanogaster lamina as a model to study Hh in survival and as a morphogen.

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