GFAPdelta in radial glia and subventricular zone progenitors in the developing human cortex.

ABSTRACT

A subpopulation of glial fibrillary acidic protein (GFAP)-expressing cells located along the length of the lateral ventricles in the subventricular zone (SVZ) have been identified as the multipotent neural stem cells of the adult mammalian brain. We have previously found that, in the adult human brain, a splice variant of GFAP, termed GFAPdelta, was expressed specifically in these cells. To investigate whether GFAPdelta is also present in the precursors of SVZ astrocytes during development and whether GFAPdelta could play a role in the developmental process, we analyzed GFAPdelta expression in the normal developing human cortex and in the cortex of foetuses with the migration disorder lissencephaly type II. We demonstrated for the first time that GFAPdelta is specifically expressed in radial glia and SVZ neural progenitors during human brain development. Expression of GFAPdelta in radial glia starts at around 13 weeks of pregnancy and disappears before birth. GFAPdelta is continuously expressed in the SVZ progenitors at later gestational ages and in the postnatal brain. Co-localization with Ki67 proved that these GFAPdelta-expressing cells are able to proliferate. Furthermore, we showed that the expression pattern of GFAPdelta was disturbed in lissencephaly type II. Overall, these results suggest that the adult SVZ is indeed a remnant of the foetal SVZ, which develops from radial glia. Furthermore, we provide evidence that GFAPdelta can distinguish resting astrocytes from proliferating SVZ progenitors.