Elusive radial glial cells: historical and evolutionary perspective

Since the discovery of radial glial cells in the human fetal forebrain, this specialized cellular population has been identified in most regions of the vertebrate brain during restricted developmental periods. However, their size, longevity, and significance for guiding migrating neurons have increased with the evolutionary expansion of the mammalian neocortex, reaching a peak in the gyrencephalic human forebrain. The phenotypic distinction of radial glial cells from the more specialized neuronal progenitors in the proliferative zones and from the migrating neurons in the intermediate zone of the primate fetal forebrain, based initially on morphological criteria, has been supported by their ultrastructural, molecular, and physiological characteristics. In addition, modern in vivo and in vitro approaches revealed that these specialized embryonic cells can also generate neuronal cell lines, which either immediately, or after several divisions, migrate along radial shaft processes of the mother cells that span the expanding and convoluted cerebral wall. The multiple functions of radial glial cells and their species-specific adaptations indicate a pivotal role in evolution, development, and pathology of the cerebral neocortex.