The choroid plexuses and their impact on developmental neurogenesis

Abstract

During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development.

Keywords: cerebral cortex; cerebrospinal fluid; choroid plexus; development; neural stem cells; neurogenesis.

Figure 1

The choroid plexuses, CSF and the neural stem cells during development. Schematic drawing showing the prime location of the choroid plexuses inside the cerebral ventricles and the bathing of the neural stem cells with CSF and molecules within it. CSF, cerebrospinal fluid.

Figure 2

The location and structure of the choroid plexuses and the blood-CSF barrier. (A,C) Schematic drawings of an embryonic brain in sagittal (A) and coronal (C) orientation depicting the location of the lateral, third and fourth ventricular choroid plexuses (LV ChP, 3V ChP and 4V ChP). (B,D) schematic drawing of the lateral and fourth ventricular choroid plexuses. (E) Simplified schematic depiction of the blood-CSF barrier and the transfer and secretion of molecules into CSF. ChP, choroid plexus.

Figure 3

The specification, differentiation and growth of the lateral ventricular choroid plexuses. (A) Photographs of transthyretin (Ttr) in situ hybridization sections, showing the choroid plexus anlage at E19, E11 and E12. (B) Schematic drawing showing the localization of the lateral ventricular choroid plexus and the cortical hem within the invaginated dorsal midline. (C) Schematic drawing (modified from Liddelow et al., 2010) showing the localization of the progenitor cells and the mode of growth of the choroid plexus.

Figure 4

Simplified schematic drawing of how choroid plexus mediated changes in CSF composition differentially alters the behavior of the neural stem cells along the neuroaxis via differences in their ability to respond (here exemplified by the presence and density of receptors).