Immunohistochemical markers of stem/progenitor cells in the developing human cerebral cortex

The development of the human cerebral cortex represents a delicate moment of embryogenesis. The ventricular zone (VZ) and the subventricular zone (SVZ) are considered the “stem/progenitor cells niches” of the developing cerebral cortex. As the majority of studies of brain development have been focused mainly on animal models, this study was focused on normal human cerebral cortex development, in particular on the stem/progenitor cells markers that may play a key role during human corticogenesis. To this end, samples from cerebral cortex were obtained from 20 human fetuses from 9 up to 40 weeks of gestation. Each sample was formalin-fixed, paraffin embedded and immunostained with several markers including WT1, Sox2, Pax6, Vimentin, Nestin, Sox11, Pax2, NF, NSE, Synaptophysin, GFAP and S100B. Five important markers of radial glial progenitor cells were evidenced during the first half of gestation: Sox2, Pax6, Vimentin, Nestin and WT1. Vimentin, Nestin and WT1 were expressed in radial glia fibers which represent the most important guide for the radial migration of newborn neurons. Instead, Pax6 immunoreactivity was detected in the VZ and SVZ, being express in radial glia cell bodies. Sox2 was expressed by the stem/progenitor cells of the VZ and SVZ including radial glia and intermediate progenitor cells, and by migrating newborn neurons. Pax2 and Sox11 expression were detected in the progenitor cells of VZ and SVZ, and in the migrating newborn neurons. Immunoreactivity for S100B, GFAP, NF and Synaptophysin, was mild or totally absent in the first half of gestation. These data reflect the lack of maturation of glial and neuronal cells in the early phases of human corticogenesis. Future studies are needed to detect differences in the mRNA expression patterns of these markers in order to better evaluate their role in cell proliferation and differentiation during human intrauterine development.