Embryonic and early fetal development of the human neocortex

Early corticogenesis was studied in human embryos and early fetuses from Ca rnegie stages 16 to 22 (5-8 gestational weeks) by using immunohistochemistr y for Reelin (Reln), calretinin (CR), and glutamic acid decarboxylase (GAD) . A first population of Reln-positive cells appears in the neocortical anla ge at stage 16 and increases in number at stages 17-18. At stages 19-20, a monolayer of horizontal CR- and GAD-positive, Reln-negative neurons forms i n the preplate, whereas Reln-positive cells shift into a subpial position. Another cell class, the pioneer projection neuron, is CR- positive but GAD- and Reln-negative; pioneer cells contribute early corticofugal axons. Pion eer cells first appear below the monolayer at stage 20 and form a pioneer p late at stage 21. The cortical plate (CP) proper emerges at stage 21 and in serts itself within the pioneer plate, which is thus split into a minor sup erficial component and a larger deep component that presumably corresponds to the subplate. Initial CP neurons are radially organized and mostly CR-ne gative. Reln-positive cells remain consistently segregated from the pioneer cells and are thus not directly involved in preplate partition. Our data i ndicate that the neuronal composition of the human neocortical preplate is more complex than generally described and that various neurons participate in a sequence of events that precede the emergence of the CP.