Exploring a Nuclear Insulin Receptor Signalling Pathway in Drosophila Neural Stem Cells
type: CreativeWork
description: The insulin receptor (InR) is a central regulator of metabolism, growth, and proliferation in both humans and *Drosophila*. Integrating a range of signals, InR coordinates pleiotropic, tissue‐specific outputs. Neural stem cells (NSCs) give rise to the vast range of cell types that comprise the central nervous system (CNS) in a manner highly regulated in both space and time. With a comparatively simple CNS that nonetheless exhibits remarkable biological conservation, combined with superior genetic tractability, *Drosophila melanogaster* is an ideal model organism for studying the principles of neurogenesis and NSC biology. In *Drosophila*, insulin signalling is necessary and sufficient for the reactivation of NSCs from quiescence, a conserved state of mitotic dormancy. InR has been observed in the nucleus of a range of cell types *in vitro* for decades, but it is only more recently that the significance of this is becoming clear. Data reveal a novel nuclear arm of the insulin signalling pathway, in which InR associates with chromatin genome‐wide, strongly localizing to promoters and activating the transcription of relevant genes. This finding represents a growing paradigm shift, encompassing other receptor tyrosine kinases (RTKs), whereby direct nuclear signalling complements canonical membrane‐localised signal transduction. Given the complexity of insulin signalling and its dysregulation across an array of chronic human diseases, this nuclear pathway constitutes an exciting avenue for basic and translational science. Characterising the nuclear actions of InR might offer a more complete understanding of the longer‐term effects of insulin signalling. In the context of the CNS, it may offer a more complete understanding of NSC dynamics, which in turn may guide future therapeutic strategies for brain repair and difficult‐to‐treat malignancies. In this thesis, nuclear insulin signalling in *Drosophila* NSCs is studied via a variety of *in vivo* methods. Cyan fluorescent …
abstract: The insulin receptor (InR) is a central regulator of metabolism, growth, and proliferation in both humans and *Drosophila*. Integrating a range of signals, InR coordinates pleiotropic, tissue‐specific outputs. Neural stem cells (NSCs) give rise to the vast range of cell types that comprise the central nervous system (CNS) in a manner highly regulated in both space and time. With a comparatively simple CNS that nonetheless exhibits remarkable biological conservation, combined with superior genetic tractability, *Drosophila melanogaster* is an ideal model organism for studying the principles of neurogenesis and NSC biology. In *Drosophila*, insulin signalling is necessary and sufficient for the reactivation of NSCs from quiescence, a conserved state of mitotic dormancy. InR has been observed in the nucleus of a range of cell types *in vitro* for decades, but it is only more recently that the significance of this is becoming clear. Data reveal a novel nuclear arm of the insulin signalling pathway, in which InR associates with chromatin genome‐wide, strongly localizing to promoters and activating the transcription of relevant genes. This finding represents a growing paradigm shift, encompassing other receptor tyrosine kinases (RTKs), whereby direct nuclear signalling complements canonical membrane‐localised signal transduction. Given the complexity of insulin signalling and its dysregulation across an array of chronic human diseases, this nuclear pathway constitutes an exciting avenue for basic and translational science. Characterising the nuclear actions of InR might offer a more complete understanding of the longer‐term effects of insulin signalling. In the context of the CNS, it may offer a more complete understanding of NSC dynamics, which in turn may guide future therapeutic strategies for brain repair and difficult‐to‐treat malignancies. In this thesis, nuclear insulin signalling in *Drosophila* NSCs is studied via a variety of *in vivo* methods. Cyan fluorescent …
author: Brace, Maire
language: eng
keywords: Drosophila, Insulin signalling, Neural stem cells
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/df867054-d0d9-47c4-823d-8274f9129326/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-07-18
date modified: 2026-07-22T22:24:01Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.107975