Team
team manager Davy Alice
Presentation
Research in the team focuses on elucidating mechanisms that govern development of the brain and the eye and how genetic or environmental alterations of these complex developmental processes may lead to disease. Our studies combine in vivo experimentations on genetic mouse models and in vitro experimentations on tissue explants and hiPSC-derived organoids.
Project 1
The ability of a single population of stem cells to give rise to distinct progeny in a spatially and temporally controlled manner is a powerful mechanism to generate cellular diversity. In this context, we study specific signaling and metabolic pathways that operate in neural progenitors to control the production of distinct types of neurons and glial cells. Currently, we focus on i) Eph:ephrin signaling and ii) one carbon metabolism.
Project 2
Astrocytes participate in a wide variety of complex and essential functions in the central nervous system (CNS), including synaptic development and plasticity, trophic regulation and blood-brain barrier formation. Work over the last decades has highlighted the existence of a far greater level of heterogeneity among astrocytes than previously considered. However, the contribution of this diversity to normal CNS function and in disease is still unclear. Recent work led us to evidence an unidentified sub-population of astrocytes (Olig2-AS) in mouse that can be distinguished from other astrocyte populations by the expression of Olig2. Our goal is to approach the question of the functional specificity of this Olig2-AS subpopulation. Experimental approaches we use in the lab include gene profiling, cellular/behavioural analysis in transgenic mouse models and in vitro models of astrocytes derived from hiPSCs.
Project 3
In the last few years hiPSC derived organoids have become indispensable models for studying neurodevelopmental processes in a human context and for assessing the developmental consequences of pathogenic gene variants. Our objectives are to develop pre-clinical models using hiPSC-derived organoids. Currently, we develop i) chimeric organoids to model CranioFrontonasal syndrome and ii) Optic vesicle brain organoids for testing VUS (variants of unknown significance) in genes required for eye development.
Project 4
Glioma initiating cells and neural stem cells (NSC) present similarities, both at the molecular and functional level. Our objectives are i) to understand the molecular mechanisms that regulate maintenance of NSCs as they might enlighten us on possible strategies to disrupt growth and/or self-renewal of glioma stem cells and ii) to characterize the contribution of diverse types of astrocytes to cancer initiation and progression.
Team members
– Plaisancié J, Chesneau B, Fares-Taie L, Rozet JM, Pechmeja J, Noero J, Gaston V, Bailleul-Forestier I, Calvas P, Chassaing N. (2024) Structural Variant Disrupting the Expression of the Remote FOXC1 Gene in a Patient with Syndromic Complex Microphthalmia. Int J Mol Sci. 25:2669. doi: 10.3390/ijms25052669.
– Saha S, Jungas T, Ohayon D, Audouard C, Tse Y, Fawal MA and Davy A. (2023) Dihydrofolate reductase activity controls neurogenic transitions in the developing neocortex. Development. 150:dev201696. doi: 10.1242/dev.201696
– Roussat M, Jungas T, Audouard C, Omerani S, Medevielle F, Agius E, Davy A, Pituello F and Bel-Vialar S. (2023) Control of G2 Phase duration by CDC25B modulates the switch from direct to indirect neurogenesis in the neocortex. J. Neurosci. 43:1154-1165. doi:10.1523/JNEUROSCI.0825-22.2022.
– Badouel C., Audouard C. and Davy A. (2022) Heterogeneity in the size of the apical surface of cortical progenitors. Developmental Dynamics. 252:363-376. doi: 10.1002/dvdy.539
– Fawal MA, Jungas T and Davy A. (2021) Inhibition of DHFR targets the self-renewing potential of brain tumor initiating cells. Cancer Lett., 503:129-137. doi: 10.1016/j.canlet.2021.01.026
– Ohayon D, Aguirrebengoa M, Escalas N, Jungas T and Soula C. (2021) Transcriptome profiling of the Olig2-expressing astrocyte subtype reveals their unique molecular signature. iScience. 24:102806. doi: 10.1016/j.isci.2021.102806
– Fawal MA, Jungas T, Kischel A, Audouard C, Iacovoni J and Davy A. (2018) Crosstalk between one carbon metabolism and Eph signaling promotes neural stem cells differentiation. Cell Reports. 23:2864-2873. doi: 10.1016/j.celrep.2018.05.005
– Aulestia FJ, Néant I, Dong J, Haiech J, Kilhoffer MC, Moreau M and Leclerc C. (2018) Quiescence status of glioblastoma stem-like cells involves remodelling of Ca2+ signalling and mitochondrial shape. Sci Rep 8:9731.
Funding
Affiliation
