Prasad, Anadika Rajive; (2024) Exploring mechanisms that regulate neuronal differentiation and neuronal numbers in the Drosophila visual system. Doctoral thesis (Ph.D), UCL (University College London).

Text Prasad_10199039_Thesis.pdf Access restricted to UCL open access staff until 1 November 2025. Download (19MB)

Abstract

Most nervous systems have a modular architecture. Connections within and between neurons arranged in layers and columns generate circuits which perform fundamental computations. Before these circuits can be formed, neurons need to be specified at the correct time and in precise numbers. Coordinating these processes within and across regions of the brain is no mean feat and requires constant communication. I use the lamina neuropil of the Drosophila visual system to explore how neurons differentiate, how their numbers are set and the molecular mechanisms that enable neuronal differentiation. The lamina consists of ~800 columns. Each column has five lamina neuron subtypes that differentiate in response to the activation of the MAPK pathway. Although each column has six precursors, only five will differentiate into the lamina neuron sub-types (L1-L5); the extra precursor is killed off by apoptosis. I first show that a glial population called the outer chiasm giant glia (xgo) secretes two ligands to induce the differentiation of L5 neurons in response to Epidermal Growth Factor from the photoreceptors. By forcing neuronal differentiation in the lamina, I uncovered that the extra precursor is specified as an L5. Therefore, each column has two L5 precursors but only one differentiates during normal development. I found that the precursors that receive the signals from glia first, will differentiate into L5s and in turn, will antagonize the differentiation of the extra precursors, resulting in their death. Finally, I showed that precursors in the lamina are primed with neuronal transcripts which are translationally repressed. Inhibiting miR-279/996 activity overcomes the repression kickstarting a neuronal differentiation programme in the lamina. Interestingly, increasing translation also drives premature neuronal differentiation, suggesting that robust cell fate changes require coordinated transcriptional and post-transcriptional regulation, including at the level of mRNA and protein synthesis. In conclusion, my results indicate that non-autonomous signals reliably pattern the lamina and drive neuronal differentiation through post-transcriptional regulation.

Download activity - last month

Export as XMLCSVJSON

Download activity - last 12 months

Export as XMLJSONCSV

Downloads by country - last 12 months

Export as CSVJSONXML

Archive Staff Only

View Item