The Autonomous Roles of Periventricular Angiogenesis in the CNS

描述（由申请人提供）：中枢神经系统（CNS）通过血管生成获得其血管系统，这是一个由现有血管或血管丛中的内皮细胞增殖并导致新血管形成的过程。脑血管化的概念通常将中枢神经系统血管生成描述为主要由氧气需求驱动的被动过程，以满足不断增长的神经元群的代谢需求。他们将发育中的内皮网络视为同质群体。我们的工作挑战了这些观念，并表明基于解剖位置，独立的生长模式和发育调节，远端脑血管分为两类：头动脉和室周血管。神经管作为血管模式的纽带，指导围绕它的脑髓血管的形成。在胚胎第9天（E9），主血管不显示发育梯度，并包围整个端脑。另一方面，心室周围血管是位于基底节区原基上的基底血管的分支，它很可能是由E9在颈区产生的咽弓动脉。在同型盒转录因子的调控下，脑室周围血管网络通过E11向背端脑以有序的点阵模式传播。该应用将验证心室周围内皮细胞为胚胎端脑后期形成神经元梯度提供关键线索的中心假设。它旨在强调心室周围内皮细胞发育的自主性，以及它是如何独立于神经元发育而调节的。它探讨了一个新的概念，即心室周围内皮细胞有一个自己的议程，具有显著的多功能性，能够塑造神经元网络。它试图挖掘心室周围内皮细胞的巨大潜力，作为在许多不同情况下恢复神经功能的治疗来源。研究结果将对血管生成调控的概念和机制产生深远影响，为端脑组织发生原理提供新的视角，并将对许多神经系统疾病的治疗产生前所未有的影响。

DESCRIPTION (provided by applicant): The central nervous system (CNS) acquires its vasculature by angiogenesis, a process consisting of proliferation of endothelial cells in existing blood vessels or vascular plexuses, and leading to the formation of new blood vessels. Notions of cerebral vascularization often depict CNS angiogenesis as a passive process driven primarily by demands of oxygen and to meet the metabolic needs of growing neuronal populations. They treat the developing endothelial network as a homogenous population. Our work has challenged these notions and shown that telencephalic blood vessels fall into two categories: pial and periventricular, based on anatomical location, independent growth patterns and developmental regulation. The neural tube acting as a vessel patterning nexus, directs the formation of the pial vessels that encompass it. The pial vessels do not display developmental gradients and are present circumscribing the entire telencephalon by embryonic day 9 (E9). The periventricular vessels on the other hand are branches of a basal vessel located in the basal ganglia primordium that likely arises from the pharyngeal arch arteries in the cervical region by E9. The periventricular vessel network propagates in an orderly lattice pattern into the dorsal telencephalon by E11 regulated by homeobox transcription factors. This application will test the central hypothesis that periventricular endothelial cells provide critical cues for the establishment of later forming neuronal gradients in the embryonic telencephalon. It aims at highlighting the autonomy of periventricular endothelial cell development and how it is regulated independently of neuronal development. It explores the novel concept that periventricular endothelial cells have an agenda of their own with remarkable versatility in being able to sculpt neuronal networks. It attempts to tap into the tremendous potential of periventricular endothelial cells as a therapeutic source for recovery of neurological function in many diverse scenarios. Results will have far-reaching effects on concepts and mechanisms of regulation of angiogenesis, offer new perspectives on telencephalic histogenesis principles and will lead to discoveries with unprecedented implication for treatment of many neurological disorders.