Adult human subventricular, subgranular, and subpial zones contain astrocytes with a specialized intermediate filament cytoskeleton

Human glial fibrillary acidic protein-δ (GFAP-δ) is a GFAP protein isoform that is encoded by an alternative splice variant of the GFAP-gene. As a result, GFAP-δ protein differs from the predominant splice form, GFAP-α, by its C-terminal protein sequence. In this study, we show that GFAP-δ protein is not expressed by all GFAP-expressing astrocytes but specifically by a subpopulation located in the subpial zone of the cerebral cortex, the subgranular zone of the hippocampus, and, most intensely, by a ribbon of astrocytes following the ependymal layer of the cerebral ventricles. Therefore, at least in the sub ventricular zone (SVZ), GFAP-δ specifically marks the population of astrocytes that contain the neural stem cells in the adult human brain. Interestingly, the SVZ astrocytes actively splice GFAP-δ transcripts, in contrast to astrocytes adjacent to this layer. Furthermore, we show that GFAP-δ protein, unlike GFAP-α, is not upregulated in astrogliosis. Our data therefore indicate a different functional role for GFAP-δ in astrocyte physiology. Finally, transfection studies showed that GFAP-δ protein expression has a negative effect on GFAP filament formation, and therefore could be important for modulating intermediate filament cytoskeletal properties, possibly facilitating astrocyte motility. Further studies on GFAP-δ and the cells that express it are important for gaining insights into its function during differentiation, migration and during health and disease. © 2005 Wiley-Liss, Inc.