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.
Ependymal cells (E cells) are responsible for the generation and organization of cerebrospinal fluid (CSF) flow through the ventricular system of the central nervous system to clear waste, guide migrating adult-born neurons and prevent hydrocephalus. However, work from the Alvarez-Buylla lab has shown that biciliated `E2 cells' exist in sparse numbers in the lateral ventricles, and recent data from the lab has identified an organized epithelium in the fourth ventricle made up exclusively of E2 cells, whose function is unknown. I propose to test the hypothesis that E2 cells convey molecular information from the CSF to modulate the neural circuits that control adult neurogenesis.
