The Autonomous Roles of Periventricular Angiogenesis in the CNS

描述(申请人提供)：中枢神经系统(CNS)通过血管生成获得血管生成，这是一个由现有血管或血管丛中的内皮细胞增殖组成的过程，并导致新血管的形成。脑血管化的概念通常将中枢神经系统血管生成描述为一个被动的过程，主要由氧气需求驱动，以满足不断增长的神经元群体的新陈代谢需求。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概念，并表明端脑血管根据解剖位置、独立的生长模式和发育调节分为两类：软脑膜血管和脑室周围血管。神经管起着血管构图网络的作用，指导着围绕它的软膜血管的形成。软膜血管不显示发育梯度，在胚胎第9天(E9)存在，包围了整个端脑。另一方面，脑室周围血管是位于基底节原基的基底血管的分支，可能在胚胎9岁时从颈部的咽弓动脉发出。脑室周围血管网络通过E11在同源框转录因子的调控下以有序的格子模式传播到背侧端脑。这一应用将检验中心假设，即脑室周围内皮细胞为在胚胎端脑中建立后来形成的神经元梯度提供关键线索。它的目的是强调脑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。它探索了新的概念，即脑室周围内皮细胞有自己的议程，能够塑造神经元网络，具有非凡的多功能性。它试图挖掘脑室周围内皮细胞的巨大潜力，在许多不同的情况下作为神经功能恢复的治疗来源。这些结果将对血管生成的调控概念和机制产生深远的影响，为端脑组织发生原理提供新的视角，并将导致对许多神经疾病的治疗具有前所未有的意义的发现。

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.