CSF secretion and flow. The CSF is secreted by the choroid plexus, a tissue located in each ventricle in the brain. CSF flows from the lateral ventricles to the third and fourth ventricles, then into the subarachnoid space of the brain and spinal cord via openings (foramena) below the cerebellum. CSF is then resorbed into the peripheral circulation by arachnoid granulations in venous sinuses of the brain.

Overview of ChP-CSF–brain interactions. In addition to secreting CSF, ChP epithelial cells secrete morphogens and proteins with sites of action within the ChP (e.g., Shh on vasculature and ChP progenitor cells) and beyond the ChP on neural stem cells (e.g., IGF2 on cerebral cortical progenitor cells, and cytokines on adult neural stem cells). The ChP can be the site of tumorigenesis (brown). It also plays a role in protecting the brain from Aβ toxicity. Because there is an exchange between the brain's interstitial fluid and CSF (perforated line), the ratio of phosphorylated Tau:Aβ provides an early diagnostic for Alzheimer's disease and can predict the severity of neurodegenerative decline. Recent advances have made possible the engineering and production of ES-derived ChP epithelial cells (green).

ChP-secreted signals instruct neurogenesis. A, In the developing embryonic brain, the ChP secretes a library of signaling activities, including insulin-like growth factor 2 (IGF2). CSF-IGF2 binds to the apical surface of cerebral cortical progenitor cells (neuroepithelial cells [NEC]; radial glial cells [RG]) located in the ventricular zone (VZ) immediately adjacent to the CSF, and to their primary cilia (arrowhead), which extend into the CSF. CSF-IGF2 instructs progenitor cell division in an age-dependent manner. B, In the adult brain, the ChP secretes many factors into the CSF, including the cytokine IL-1β. CSF-IL-1β regulates the quiescence of adult neural stem cells (B cells), which contact the CSF via a primary cilium (arrowhead), while retaining contact with blood vessels (BV). E, Ependymal cells; C, transit amplifying cells; A, neuroblasts.