Development of Choroid Plexus and the Blood-CSF Barrier

描述(申请人提供)：血-组织屏障保护中枢神经系统，代表中枢神经系统和外周循环之间的主要界面。屏障的破坏会导致长期的神经毒性，导致许多神经系统疾病的发展。屏障存在于脑内皮细胞、脉络丛上皮和蛛网膜上皮中。药物对中枢神经系统的暴露部分取决于血-脑和血-脑脊液屏障提供的物理屏障，以及底物对位于这两个界面的特定运输系统的亲和力。脉络丛上皮、蛛网膜上皮和脑室周围器官共同构成血-脑脊液屏障。脉络丛参与脑脊液的产生和分泌。我们对脉络丛发育生物学的了解非常有限。拟议的研究旨在探索脉络丛形成的分子和细胞机制。更具体地说，结合分子、细胞和胚胎学方法，脉络丛的形态发生和成熟以及指导其形成和建立屏障功能的机制将在发育中的动物和基于细胞培养的分析中得到解决。我们的总体目标是提供脉络丛的全面特征，脉络丛是血-脑脊液屏障的中心成分，也是大脑中一个重要但被忽视的结构，1它可能被探索为治疗神经疾病的药物和基因输送策略的目标。

DESCRIPTION (provided by applicant): Blood-tissue barriers protect the central nervous system and represent the major interfaces between the central nervous system and peripheral circulation. Damage to the barriers leads to long-term neurological toxicity in the development of many neurological diseases. Barriers are found in the brain endothelium, the choroid plexus epithelium, and the arachnoid epithelium. Drug exposure to the CNS is partially dependent on the physical barrier presented by the blood-brain and blood-CSF barrier and the affinity of the substrate for specific transport systems located at both of these interfaces. The choroid plexus epithelium, together with the arachnoid epithelium and the circumventricular organs collectively constitute the blood-CSF barrier. The choroid plexus is involved in the production and secretion of CSF. Our understanding of choroid plexus developmental biology is extremely limited. The proposed studies aim at exploring the molecular and cellular mechanisms underlying the formation of the choroid plexus. More specifically, using a combination of molecular, cellular and embryological approaches, morphogenesis and maturation of the choroid plexus and the mechanisms that guide its formation as well as the establishment of its barrier functions will be addressed in the context of the developing animal and in cell culture-based assays. Our general aim is to provide a comprehensive characterization of the choroid plexus, the central element of the blood-CSF barrier and an important, yet overlooked structure in the brain, 1 that may be potentially explored as a target for drug and gene delivery strategies for the treatment of neurological diseases.