Exploring the evolutionary origins of gene regulatory networks cotrolling neurogenic system development in Drosophila melanogaster

Lead Research Organisation: University of Leicester
Department Name: College of Lifesciences

Abstract

Embryonic neurogenesis requires cell differentiation programmes to be tightly regulated across space and time. Elucidating the spatiotemporal gene expression patterns of the regulatory genes. Involved in neurogenic development is important for understanding how these systems developed. Delineating the transcriptional program underscoring its development should enable us to recapitulate the patterns of embryonic expression that provide an improved view of how these systems function in a wide variety of neuronal functions, including behaviour. This project is developed with the goal to characterise the spatiotemporal combination of transcription factor expression, and the cascade of lineage and time-specific transcription factors that are involved in cell fate specification and differentiation.
GRNs are defined as the suite of regulatory genes, along with their regulators, that control transcriptional dynamics within a cell. The project is designed to utilise single-cell sequencing technologies, sampling across critical developmental timepoints of embryonic neuronal development in Drosophila melanogaster, to identify all the molecular players and the temporal patterning of the gene regulatory networks (GRNs) that control the differentiation process for each neuronal subtype. The single-cell data analysis is supplemented with experimental validation using transcript-hybridisation experiments of the transcriptional factors regulating neurogenic development to analyse spatiotemporal organisation. Furthermore, in order to determine causative effect of these regulatory genes, perturbation experiments using CRISPR and RNAi transgenics are performed to analyse the role of each regulatory gene on other genes within its GRN and fundamentally the developmental process of each neuronal subtype. These time-resolved gene expression maps help to establish a high-resolution spatiotemporal profile of the regulatory code underlying neuronal subtype specification and differentiation.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/T00746X/1 01/10/2020 30/09/2028
2432672 Studentship BB/T00746X/1 05/10/2020 04/10/2024 Clifton Lewis