Functional identities of distinct ventricular ependymal cells.

室管膜细胞(E细胞)是脑脊液(CSF)流动和预防脑积水所必需的。脑脊液流动被认为可以调节颅内压，促进废物清除，但它可能起到更大的作用。最近的几项研究表明，脑脊液中含有神经内分泌信号、神经发生、迁移和脑活动所必需的信号分子。脑脊液不断地由E细胞在脑室系统中产生和移动，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层均匀的多纤毛(E1)细胞组成的，但最近的数据表明E细胞是异质的。Alvarez-Buylla(A.-B.)实验室发现了一种新的E细胞亚型(E2细胞)，它具有独特的顶端结构域，只有两个运动型(9-2微管结构)纤毛，以及比E1细胞大30-100倍的复杂基底。此外，最近出版的数据显示，E2细胞有长的基底突起，投射到下面的脑实质，包括中缝背核(DRN)。A.-B.实验室之前已经表明，DRN调节B1细胞成年神经发生。脑实质中的大多数神经元和神经胶质细胞体与脑脊液直接接触是分开的。我怀疑，E2细胞可能是脑室和脑实质隔间之间的桥梁；它们的顶端隔室具有大的基底体和长长的活动纤毛，可以用来检测脑脊液成分；它们漫长的基底突起可以将这一信息传递给潜在的神经元。我假设，E2细胞在空间和结构上已经准备好‘弥合’脑脊液和DRN神经元之间的信号分子之间的差距，而依赖DRN的成人神经发生受E2细胞信号的调控。在目标1中，我将检验E2细胞基本突起在出生后发育过程中达到形态成熟的假设，并与DRN神经元进行接触。在目标2中，我将测试E2细胞调节DRN环路动力学和成人神经发生的假设。我预测，当选择性地切除接触DRN的E2细胞时，神经发生的速度将会改变。

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.