How to build a nervous system? Understanding the genetic control of neurogenesis in Drosophila melanogaster: Insights using Comparative and Systematic Approaches

Neurogenesis, the process by which neurons are generated, is governed by complex gene regulatory networks (GRNs) that integrate signalling pathways and transcription factors (TFs) to coordinate neural development. This thesis explores the evolutionary conservation and divergence of neurogenic GRNs across metazoans, with a focus on the GRNs controlling apical organ neurogenesis in Strongylocentrotus purpuratus and their potential conservation in other metazoan species. In addition, the thesis explores the temporal and regulatory dynamics of neuronal subtype specification in Drosophila melanogaster, offering detailed insights into this critical phase of neurogenesis.

Chapter 2 examines the GRN responsible for apical organ development in S. purpuratus, revealing a set of conserved TFs and signalling pathways, including Sox and Delta/Notch, which are pivotal for early neural specification. While the entire GRN is not universally conserved across metazoans, specific components and their regulatory functions show significant evolutionary conservation. Chapter 3 focuses on the optimisation of single-cell RNA sequencing (scRNAseq) in Drosophila embryos, which enables the high-resolution profiling of gene expression dynamics during embryonic neurogenesis. Building on this dataset, Chapter 4 investigates the specification of monoaminergic neurons in Drosophila, identifying key TFs and temporal regulatory mechanisms, such as Lmx1a and otp TFs, involved in the differentiation of dopaminergic and serotonergic neurons.

This thesis underscores the evolutionary robustness of specific neurogenic regulatory mechanisms while also highlighting functional divergences that enable species-specific adaptations. By integrating comparative biology with advanced molecular techniques, this work enhances our understanding of the molecular mechanisms driving neurogenesis and provides new insights into the evolution of nervous system complexity, particularly within the monoaminergic system.