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Regulation of neural stem cell quiescence and reactivation

Supervisor: Andrea Brand

Neural stem cells in the adult brain exist primarily in a quiescent state but can be reactivated in response to changing physiological conditions. How do stem cells sense and respond to metabolic changes? In the Drosophila central nervous system, quiescent neural stem cells are reactivated synchronously in response to a nutritional stimulus. We discovered that feeding triggers insulin production by blood-brain barrier glial cells, activating the insulin/IGF pathway in underlying neural stem cells and stimulating their growth and proliferation. We showed that gap junctions in the blood-brain barrier glia mediate the influence of metabolic changes on stem cell behaviour, enabling glia to respond to nutritional signals and reactivate quiescent stem cells.

This project will investigate the systemic and local signals that regulate stem cell growth and proliferation and the role of glia in inducing neural stem cell exit from quiescence. It will take advantage of ‘Targeted DamID’, a technique we developed to enable cell type-specific transcriptional profiling in intact organisms, without cell isolation. Targeted DamID also permits genome-wide profiling of DNA- or chromatin-binding proteins.

Relevant references

Marshall, O.J. and Brand, A.H. (in press). Novel changes in chromatin state during neural development revealed by in vivo cell-type specific profiling. Nature Communications.

Marshall O.J., Southall T.D., Cheetham S.W. and Brand A.H. (2016). Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing. Nature Protocols 11(9), 1586-1598.

Spéder, P. and Brand, A.H. (2014). Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells. Developmental Cell 30, 309-321.

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