Functional identities of distinct ventricular ependymal cells.

室管膜细胞（E 细胞）对于脑脊液（CSF）流动和预防脑积水至关重要。脑脊液流动被认为可以调节颅内压并促进废物清除，但它的作用可能远不止于此。最近的几项研究表明，脑脊液含有神经内分泌信号、神经发生、迁移和大脑活动所必需的信号分子。 CSF 不断地由 E 细胞产生并通过心室系统移动，在人类中每天翻转三到四次。虽然室管膜衬里被认为是由同质的多纤毛 (E1) 细胞层组成，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 倍的复杂基体。此外，最近公布的数据显示，E2 细胞具有长的基底突起，投射到底层的脑实质，包括中缝背核 (DRN)。 A.-B。实验室此前已表明 DRN 调节 B1 细胞成体神经发生。脑实质中的大多数神经元和神经胶质细胞体与脑脊液的直接接触是分开的。我怀疑 E2 细胞可能充当脑室和实质脑室之间的桥梁；它们的顶端室具有大的基体和长的活动纤毛，可以用于检测脑脊液成分；它们的长基底过程可以将这些信息传递给底层神经元。我假设 E2 细胞在空间和结构上已准备好“桥接”CSF 中的信号分子和 DRN 神经元之间的间隙，并且 DRN 依赖性成体神经发生受到 E2 细胞信号传导的调节。在目标 1 中，我将检验以下假设：E2 细胞基底突起在出生后发育过程中达到形态成熟，并在 DRN 神经元之间建立联系。在目标 2 中，我将测试 E2 细胞调节 DRN 回路动力学和成体神经发生的假设。我预测当 DRN 接触 E2 细胞被选择性消融时，神经发生率将会改变。

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.