MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis

Publication date: 15 August 2017
Source:Cell Reports, Volume 20, Issue 7
Author(s): Romain Madelaine, Steven A. Sloan, Nina Huber, James H. Notwell, Louis C. Leung, Gemini Skariah, Caroline Halluin, Sergiu P. Paşca, Gill Bejerano, Mark A. Krasnow, Ben A. Barres, Philippe Mourrain
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.

Graphical abstract

Teaser

The coordination of neuronal and vascular cell development is critical to ensure the proper formation of the vertebrate brain. Madelaine et al. show that the microRNA-9 couples neurogenesis and brain angiogenesis through the inhibition of Tlx and Onecut transcription factors regulating neuronal VEGF-A expression.


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