Project Details
Projekt
Functional analysis of ncRNAs in Drosophila nervous system development with cell type specificity and single-cell resolution
Subject Area
Human Cognitive and Systems Neuroscience
Developmental Neurobiology
Molecular Biology and Physiology of Neurons and Glial Cells
Developmental Neurobiology
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2014 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 255318231
Orderly specification and differentiation of naïve cells into progressively more complex cell types, tissues and organ systems is a fundamental principle in developmental and stem cell biology. Many key developmental regulators like transcription factors and signalling molecules have been identified over the past decades. It has become clear over the past few years, however, that a whole other critical regulatory level exists: a multitude of non-coding RNAs (ncRNAs) guide and control gene expression and convey cellular identity. It is becoming increasingly apparent, that the ncRNAs are especially important for the development and function of the nervous system.In order to understand the mechanisms by which ncRNAs drive neurogenesis, we must first establish an inventory of ncRNAs that may be involved. We have systematically identified the gene expression programs in vivo over the course of early neurogenesis and the resulting transcriptomic atlas allows insights into early Drosophila neurogenesis with unprecedented cell-type and temporal resolution. The identified ncRNAs belong to several classes, such as micro RNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs) and we have made several intriguing observations regarding the prevalence and specificity of lncRNAs and circRNAs that clearly point towards their importance in regulating cellular identity and even signalling among cells.Given the developmental and cell type resolution we have established, it is now possible to ask new kinds of questions, for example, how transcription factors are differentially deployed along developmental lineages, such as from neuroblast to neuron, how micro RNAs may effect target transcripts in a cell type specific manner, or even how neurons and glia may communicate with each other via signalling pathways. The goal now is to understand the roles of ncRNAs in neurogenesis - how they affect cell fate decisions and the mechanisms by which they do so. Drosophila is a unique system in which to ask such questions due to is unparalleled experimental accessibility, coupled with key neurogenic patterning principles conserved from flies to mice. Given the exquisite cell type specificity observed for many ncRNAs, we aim to elucidate the mechanisms by which ncRNAs function at the single-cell level.
DFG Programme
Priority Programmes
