Functional identities of distinct ventricular ependymal cells.

不同心室室管膜细胞的功能特性。

• 批准号: 9394748
• 负责人: Stephanie Redmond
• 金额: $ 5.63万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9394748
• 关键词: Ablation; Adult; Affect; Aging; Apical; Basal Cell; Brain; Caliber; Cell Death; Cell physiology; Cells; Cerebrospinal Fluid; Cilia; Collaborations; Complex; Cuboidal Cell; Data; Deoxyuridine; Detection; Development; Diphtheria Toxin; Disease; Electron Microscopy; Ependymal Cell; Epithelium; Excision; Exhibits; FOS gene; Feeding behaviors; Floor of the Fourth Ventricle; Fourth ventricle structure; G Cells; Gap Junctions; Generations; Glial Fibrillary Acidic Protein; Homeostasis; Human; Hydrocephalus; Hypothalamic structure; Injectable; Injection of therapeutic agent; Interneurons; Intracranial Pressure; Label; Microtubules; Molecular; Morphology; Motor; Mus; Nerve Degeneration; Nervous system structure; Neuraxis; Neuroglia; Neurons; Neuropil; Neurosciences; Neurosecretory Systems; Pattern; Play; Prevention; Process; Property; Radial; Role; SHH gene; Signal Transduction; Signaling Molecule; Spain; Stream; Structure; Surface; Synapses; Testing; Thinness; Third ventricle structure; Tight Junctions; Time; Tissues; Universities; Ventricular; Viral; Virus; Work; adult neurogenesis; blood glucose regulation; brain parenchyma; cell motility; cerebrospinal fluid flow; cilium motility; density; diphtheria toxin receptor; dorsal raphe nucleus; drinking water; kinetosome; lateral ventricle; migration; neural circuit; neurogenesis; novel; olfactory bulb; postnatal; prevent; ventricular system; wasting

Ependymal cells (E cells) are essential for cerebrospinal fluid (CSF) flow and prevention of hydrocephalus. CSF flow is thought regulate intracranial pressure and promote waste removal, but it’s likely doing much more. Several recent studies suggest that the CSF contains essential signaling molecules for neuroendocrine signaling, neurogenesis, migration and brain activity. The CSF is constantly being produced and moved by E cells through the ventricular system, turning over three to four times per day in humans. While the ependymal lining was thought to be composed of a homogeneous layer of multiciliated (E1) cells, recent data suggest that E cells are heterogeneous. The Alvarez-Buylla (A.-B.) lab has identified a novel subtype of E cell (E2 cell) that has a unique apical domain with only two motile-type (9+2 microtubule structure) cilia, and complex basal bodies that are 30-100 times larger than those of E1 cells. Furthermore, recent data now in press has revealed that E2 cells have long basal processes that project into the underlying brain parenchyma, including the dorsal raphe nucleus (DRN). The A.-B. lab has previously shown that the DRN modulates B1 cell adult neurogenesis. Most neuronal and glial cell bodies in the brain parenchyma are separated from direct CSF contact. I suspect that E2 cells could be serving as a bridge between the ventricular and parenchymal brain compartments; their apical compartment with large basal bodies and long motile cilia could serve for the detection of CSF components; their long basal process could transmit this information to underlying neurons. I hypothesize that E2 cells are spatially and structurally primed to `bridge' the gap between signaling molecules in the CSF and neurons of the DRN, and that DRN-dependent adult neurogenesis is modulated by E2 cell signaling. In Aim 1 I will test the hypothesis that E2 cell basal processes reach morphological maturity during postnatal development and make contacts among DRN neurons. In Aim 2 I will test the hypothesis that E2 cells modulate DRN circuit dynamics and adult neurogenesis. I predict that rates of neurogenesis will be altered when DRN-contacting E2 cells are selectively ablated.

室管膜细胞（E细胞）对于脑脊液（CSF）流动和预防脑积水是必不可少的。脑脊液流动被认为是调节颅内压和促进废物清除，但它可能做得更多。最近的几项研究表明，CSF含有神经内分泌信号传导、神经发生、迁移和脑活动的必需信号分子。CSF由E细胞通过脑室系统不断产生和移动，在人类中每天翻转三到四次。虽然室管膜衬里被认为是由一个同质层的多纤毛（E1）细胞，最近的数据表明，E细胞是异质的。阿尔瓦雷兹-布伊拉（A.- B.）实验室已经鉴定了一种新的E细胞亚型（E2细胞），其具有独特的顶端结构域，仅具有两个运动型（9+2微管结构）纤毛，以及比E1细胞大30-100倍的复杂基体。此外，最近出版的数据显示，E2细胞有很长的基底突起，这些突起投射到下面的脑实质中，包括中缝背核（DRN）。A.- B。实验室先前已经表明DRN调节B1细胞的成体神经发生。脑实质中的大多数神经元和神经胶质细胞体与直接CSF接触分离。我怀疑E2细胞可能是心室和脑实质间室之间的桥梁;它们具有大基底体和长运动纤毛的顶室可能用于检测CSF成分;它们的长基底突起可以将此信息传递给下面的神经元。我假设，E2细胞的空间和结构引发的“桥梁”之间的差距差距的信号分子在CSF和DRN的神经元，DRN依赖的成人神经发生是由E2细胞信号调制。在目的1中，我将测试的假设，E2细胞的基底进程达到形态成熟，在出生后的发展和DRN神经元之间的联系。在目标2中，我将测试E2细胞调节DRN回路动力学和成人神经发生的假设。我预测，神经发生率将被改变时，DRN接触E2细胞被选择性消融。