Where did the ventricles go?

(Pcdh) family of genes is a large subgroup within the cadherin superfamily of cell adhesion molecules. The Pcdh family is divided into clustered (Pdch-a, Pdch-b and Pdch-c genes) and non-clustered families and they are predominantly expressed in brain (Yagi 2008). There has been considerable interest in the role of the Pdch family in synaptogenesis and neuronal survival (Weiner et al. 2005). However, in a paper in this issue of Journal of Neurochem-istry, Lobas et al. (2012) have surprisingly found that all 22 of the c-Pdchs are expressed at the choroid plexus, the site of the blood–CSF barrier. In addition, they found that these c-Pdchs were present at the apical (CSF-facing) membrane of the choroid plexus epithelium, where there is very limited expectation of cell–cell contact, and that there was considerable variation in expression between individual epithelial cells. They were also surprised to find that targeted mutation of the Pcdh-c locus resulted in a marked reduction in the volumes of the cerebral ventricles, suggesting that c-Pdchs have a major impact on CSF production. Devising methods to modulate CSF formation is clinically very important, particularly with respect to hydrocephalus, and understanding the effects of c-Pdchs may help in developing new therapeutics. Currently, the principal treatment for hydro-cephalus is placement of a shunt and 40–50% of shunts fail within 2 years of surgery (Notarianni et al. 2009). It is noticeable that the reduction in ventricle volume found with targeted mutation of the Pcdh-c locus is very similar to that found in the NBCn2 KO mouse that is thought to be involved in CSF secretion (Jacobs et al. 2008). CSF secretion involves the transport of primarily Na + , Cl) and HCO 3) , and water, from blood across the choroid plexus epithelium to the cerebral ventricles (Brown et al. 2004). That vectoral transport involves a polarized distribution of ion transporters and channels at the choroid plexus epithe-lium. For example, Na +-K +-ATPase, the Na +-K +-2Cl) cotransporter, NKCC1, and the Na + /H + exchanger, NHE1, have an apical distribution (CSF facing), whereas the anion exchanger, AE2, the Na + /HCO 3)-cotransporter, NBCn1, and the Na + /Cl) /HCO 3) transporter, NBCn2, are present on the basolateral membrane (blood facing) of the epithelium (Damkier et al. 2010). Targeting specific transporters can reduce CSF production (e.g. inhibiting Na +-K +-ATPase causes marked reductions; Brown et al. 2004). Furosemide with acetazolamide (which indirectly affects transport) …