Temporal and comparative analysis of genes that play a role in brain vascular development

Abstract

Arteriovenous malformations (AVMs) are direct abnormal connections of arteries and draining veins without a capillary bed. AVMs, in which normal blood flow is interrupted, carry high risk of bleeding throughout life. They are thought to arise during development and there is very limited knowledge on the molecular pathogenesis of the AVMs. To unravel the molecular mechanisms and develop therapy modalities, detailed understanding of the brain vascular development at molecular level is crucial. Besides, today compelling number of evidence suggests that blood vessels and neurons use common signals and mechanisms to shape the nervous systems. Moreover, angiogenesis and some of its key modulators were recently shown to protect the nervous system from neurodegeneration. Thus, the knowledge of the norms of brain vascular development and the genes involved is essential for detailed understanding of the role of angiogenesis in neurodegenerative mechanisms. However, most of what we know about angiogenesis at molecular level is derived from pathological studies. In literature, there are no multi-gene level studies covering the norms of brain vascular development at molecular level. In this study, for the first-time in literature, brain vascular development was investigated using a pathway-specific, low-density microarray system in a systemic manner. Temporal and comparative expression of 113 angiogenesis-related genes was analyzed and genes that play a role in cerebrovascular development were determined. Genes like Bai1, Nudt6, Ctgf, were shown to be expressed in brain development for the first time in this study. The findings are expected to make important contributions to the limited research on brain vascular development and are expected to be an important reference for functional studies in AVM and neurodegeneration; they will also form the basis for further studies in humans.