MicroRNA-9 Couples Brain Neurogenesis and Angiogenesis

Cell Reports

James H. Notwell¹  Gill Bejerano¹  Ben A. Barres²  Steven A. Sloan²  Mark A. Krasnow³  Romain Madelaine⁴  Sergiu P. Paşca⁴  Nina Huber⁴  Gemini Skariah⁴  Philippe Mourrain⁴  Louis C. Leung⁴  Caroline Halluin⁴ 

[1] Department of Computer Science, Stanford University, Stanford, CA 94305, USA;Department of Neurobiology, Stanford University, Stanford, CA 94305, USA;HHMI and Department of Biochemistry, Stanford University, Stanford, CA 94305, USA;Stanford Center for Sleep Sciences and Medicine, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA;

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

DOI  :  10.1016/j.celrep.2017.07.051

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown