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Choroid plexus regulation of adult neural stem cells

Research Project
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01.07.2014
 - 30.06.2019

Stem cells reside in specialized niches that support their life-long self-renewal and differentiation. Adult neural stem cells continuously generate neurons in restricted parts of the brain that functionally integrate into neural circuits. These stem cells may represent an important source of endogenous cells that can be stimulated for brain repair. Defining the source and identity of signals from the niche that regulate adult neural stem cell behavior is essential to eventually harnessing these cells for brain repair, as well as understanding how changes in niche contribute to the decline in stem cell function that occurs with aging and disease. The ventricular-subventricular zone (V-SVZ) is the largest germinal region in the adult brain and is located adjacent to the cerebrospinal fluid (CSF)-filled lateral ventricles. The stem cells in the V-SVZ niche are continuously bathed by CSF. The CSF is produced by the choroid plexus, which floats in the brain ventricles. Although the lateral ventricle choroid plexus (LVCP) is in close proximity to the V-SVZ, its role in the niche has largely been ignored. We propose that in addition to important homeostatic functions, the LVCP is a key component of the adult V-SVZ NSC niche. We will investigate how LVCP secreted factors affected the behavior of adult neural stem cells and their progeny. We will also determine how aging and other states influence the functional effect of the LVCP compartment on adult neural stem cells.

Publications

Silva-Vargas, Violeta et al. (2016) ‘Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells’, Cell stem cell, 19(5), pp. 643–652. Available at: https://doi.org/10.1016/j.stem.2016.06.013.

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Fiona Doetsch

Principal Investigator