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Cell Rep. 2017 Aug 15;20(7):1533-1542. doi: 10.1016/j.celrep.2017.07.051.

MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis.

Author information

1
Stanford Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
2
Department of Neurobiology, Stanford University, Stanford, CA 94305, USA.
3
Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
4
Department of Computer Science, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.
5
HHMI and Department of Biochemistry, Stanford University, Stanford, CA 94305, USA.
6
Stanford Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA; INSERM 1024, École Normale Supérieure, Paris 75005, France. Electronic address: mourrain@stanford.edu.

Abstract

In the developing brain, neurons expressing VEGF-A and blood vessels grow in close apposition, but many of the molecular pathways regulating neuronal VEGF-A and neurovascular system development remain to be deciphered. Here, we show that miR-9 links neurogenesis and angiogenesis through the formation of neurons expressing VEGF-A. We found that miR-9 directly targets the transcription factors TLX and ONECUTs to regulate VEGF-A expression. miR-9 inhibition leads to increased TLX and ONECUT expression, resulting in VEGF-A overexpression. This untimely increase of neuronal VEGF-A signal leads to the thickening of blood vessels at the expense of the normal formation of the neurovascular network in the brain and retina. Thus, this conserved transcriptional cascade is critical for proper brain development in vertebrates. Because of this dual role on neural stem cell proliferation and angiogenesis, miR-9 and its downstream targets are promising factors for cellular regenerative therapy following stroke and for brain tumor treatment.

KEYWORDS:

Onecut; Tlx; angiogenesis; brain; human neural stem cells; miR-9; neurogenesis; neuronal VEGF-A; retina; zebrafish model system

PMID:
28813666
PMCID:
PMC5665055
DOI:
10.1016/j.celrep.2017.07.051
[Indexed for MEDLINE]
Free PMC Article

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