Format

Send to

Choose Destination
Neuron. 2014 Aug 6;83(3):572-85. doi: 10.1016/j.neuron.2014.06.015. Epub 2014 Jul 18.

Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction.

Author information

1
Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain; Departamento de Microbiología y Biología Celular, Universidad de La Laguna, 38204 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
2
Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain.
3
Departamento de Farmacología, Universidad de Valencia, 46010 Valencia, Spain.
4
Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain.
5
Departamento de Microbiología y Biología Celular, Universidad de La Laguna, 38204 San Cristóbal de La Laguna, Santa Cruz de Tenerife, Spain.
6
Centro de Investigaciones Biomédicas en Red sobre Enfermedades Neurodegenerativas, 28031 Madrid, Spain; Departamento de Biología Celular, Universidad de Valencia, 46010 Valencia, Spain. Electronic address: isabel.farinas@uv.es.

Abstract

Interactions of adult neural stem cells (NSCs) with supportive vasculature appear critical for their maintenance and function, although the molecular details are still under investigation. Neurotrophin (NT)-3 belongs to the NT family of trophic factors, best known for their effects in promoting neuronal survival. Here we show that NT-3 produced and secreted by endothelial cells of brain and choroid plexus capillaries is required for the quiescence and long-term maintenance of NSCs in the mouse subependymal niche. Uptake of NT-3 from irrigating vasculature and cerebrospinal fluid (CSF) induces the rapid phosphorylation of endothelial nitric oxide (NO) synthase present in the NSCs, leading to the production of NO, which subsequently acts as a cytostatic factor. Our results identify a novel interaction between stem cells and vasculature/CSF compartments that is mediated by an unprecedented role of a neurotrophin and indicate that stem cells can regulate their own quiescence in response to endothelium-secreted molecules.

PMID:
25043422
DOI:
10.1016/j.neuron.2014.06.015
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center