Neural stem cell plasticity
Group leader : C. Maurange
Our team investigates the molecular principles underlying modulations of neural stem cell properties during the different phases of brain building thus ensuring that all types of neurons are produced. We are also exploring the impact of suboptimal nutritional on neural stem cells, and are studying how neural stem cell properties may be hijacked during the cancerous process.
Neural stem cells found in the brain and nervous system are very plastic. This plasticity allows each one of them to generate a vast repertoire of neural and glial progeny while the brain is being built during foetal life or to regenerate neurons after brain injury. However, the mechanisms underlying this plasticity remain unclear. Our team aims at deciphering the molecular and genetic mechanisms involved. We are also trying to investigate how environmental conditions during foetal growth affect neural stem cell plasticity and their ability to constitute their full repertoire of neurons. Finally, because of their plasticity and large proliferation potential, stem cells are largely exposed to cancer-promoting defects. Our ambition therefore consists in uncovering how neural stem cell plasticity can be hijacked for the benefit of cancerous processes.
Understanding these basic principles could help correcting cellular failures responsible for cancer induction, delaying ageing and exploiting neural stem cell regenerative potential.
In order to investigate these fascinating issues, we use the fruitfly Drosophila. Work on this insect over the last 100 years has allowed for major discoveries in all fields of biology and medicine, culminating in several Nobel prizes. Indeed, many of the genes and molecular principles allowing an organism to develop from an egg have been conserved in species throughout evolution. The Drosophila adult brain, as in mammals, is mainly composed of neurons and glial cells (more than 100000) disposed in complex neural circuits. These cells have been generated in the developing animal from a limited set of progenitors called neural stem cells. We take advantage of the powerful genetic tools developed in this model organism to manipulate neural stem cells while the brain is being constructed during development. We aim at identifying the genes and molecular mechanisms controlling their properties.
Precisely, we follow three main lines of research in the lab.
We try to decipher how a genetic program, governed by a series of sequentially expressed transcription factors, known as the temporal series, is deployed in every neural stem cells to ensure that different types of neurons are generated over time. This involves transcriptomic and epigenetic studies that will help identifying genes which temporally-regulated expression controls neural stem cell proliferation and differentiation properties.
- We investigate the impact of nutritional conditions on the making of the brain. We have recently identified an adaptive strategy used by the developing brain to modulate its size according to nutritional conditions. This system allows the brain to reduce the number of neurons while preserving neuronal diversity during nutrient restriction. We are currently dissecting the mechanisms underlying this brain-sparing strategy.
- We explore the mechanisms that drive tumor progression in the Drosophila brain. Neural stem cells have the ability to divide asymmetrically. By this way, they self-renew while budding-off progeny that differentiate in neurons or glia. Some mutations perturb this division mode leading to an amplification of neural stem cell numbers at the expense of neurons. Interestingly, these supernumerary stem cells rapidly acquire cancerous properties escaping all proliferation control mechanisms. Yet the underlying process is unknown. We have devised a genetic assay that allows us to track and genetically manipulate neural stem cell-derived tumours during the different steps of cancer progression. Using this assay, we are investigating the molecular events driving cancer transformation in these neural tumours. These studies might open new avenues for the identification of novel therapeutic targets aiming at eliminating cancer stem cells that remain particularly resistant to current treatments.
March 6th, 2019
Developmental regulation of regenerative potential in Drosophila by ecdysone through a bistable loop of ZBTB transcription factors
January 25th, 2018
Two distinct mechanisms silence chinmo in Drosophila neuroblasts and neuroepithelial cells to limit their self-renewal
June 14th, 2016
Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila
March 26th, 2014
Building a brain under nutritional restriction: insights on sparing and plasticity from Drosophila studies.
March 28th, 2013
Protection of neuronal diversity at the expense of neuronal numbers during nutrient restriction in the Drosophila visual system.
February 11th, 2012
Temporal specification of neural stem cells: insights from Drosophila neuroblasts.
November 11th, 2008
Temporal control of neuronal diversity: common regulatory principles in insects and vertebrates?
May 30th, 2008
Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila.
October 1st, 2006
Signaling meets chromatin during tissue regeneration in Drosophila.
November 10th, 2005
Suppression of Polycomb group proteins by JNK signalling induces transdetermination in Drosophila imaginal discs.
January 11th, 2005
Brainy but not too brainy: starting and stopping neuroblast divisions in Drosophila.
October 15th, 2002
A cellular memory module conveys epigenetic inheritance of hedgehog expression during Drosophila wing imaginal disc development.
April 11th, 2003