T-ERC_COG - Tremplin-ERC Consolidator Grant

Integration and transmission of stress signals in the neural stem cell niche during development – SiStemNic

Submission summary

Development of a functional central nervous system at birth relies on the timely proliferation of neural stem cells. Via interactions with other cell types, neural stem cells form an intricate cellular microenvironment, the niche, which behaves both as a signalling hub and a structural scaffold. Central nervous system formation is sensitive not only to intrinsic but also to extrinsic signals. Rising concern about environmental threats has recently highlighted the potential impact of pollutants and emerging infectious agents on neurogenesis and brain development. However, how neural stem cells integrate stress signals, both at the individual and population level, and through a complex niche structure, remains mysterious.

The developing Drosophila larval central nervous system is a powerful and practical in vivo genetic model, which has become a key player in stem cell biology. It contains well characterised neural stem cells found in a multi-layered niche. Building on our pioneering models of niche morphogenesis and brain infection, and on original starting data, this proposal aims to decipher step by step how the neural stem cell niche integrates and responds to stress signals in a developing central nervous system. Specifically, we will:
1. Decode signal transmission between neural stem cells and through the complex niche architecture.
2. Elucidate the conversion of a systemic stress into a neurogenic response.
3. Identify pollution and infection-derived environmental stresses sensed by neural stem cells.

To achieve our goals, we will rely on a highly interdisciplinary approach combining complex genetic tools, live-imaging and long-term culture of whole central nervous systems, virtual reality, biophysical modelling and state-of-the art transcriptomics. This research has the opportunity to radically change how we see signal transmission in a complex neural stem cell niche under stress.

Project coordination

Pauline SPÉDER-MURPHY (INSTITUT PASTEUR)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IP INSTITUT PASTEUR

Help of the ANR 100,005 euros
Beginning and duration of the scientific project: June 2022 - 24 Months

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