Developmental changes in layer I of the human neocortex during prenatal life: a DiI-tracing and AChE and NADPH-d histochemistry study.

The development of fetal layer I (marginal zone, MZ) was studied in the human neocortex by using DiI tracing and AChE and NADPH-d histochemistry, and examining the Nissl-stained material of the Yakovlev Collection. We describe the sequential maturation of the Cajal-Retzius (CR) cells and the granule cells of the subpial granular layer (SGL), and the close relationship between both. The first CR cells appear in the primordial plexiform layer, at 6 gestational weeks (GW). After the formation of the cortical plate, they settle under the pial surface. At 13 GW, the SGL begins to form around the CR cells. The horizontal members of a polymorphic population of CR cells begin to mature at 13 GW, and the intermediate and vertical forms differentiate at 16 and 18 GW, respectively. All CR cells project into an axonal plexus in the lower third of the MZ. From 18 GW, CR cells and SGL become segregated, and the polymorphic CR cells lie now below the SGL, with which they remain connected by ascending processes. Granule cells invade the lower MZ contacting somata and processes of CR cells. The somata of vertical CR cells elongate until 23/24 GW when they show degenerative signs. After 24 GW, all polymorphic CR cells die. Granule cells degenerate after 24 GW; the SGL disappears at 28/30 GW. A population of persisting CR cells, morphologically different from the transient polymorphic forms, appears in a subpial position and survives in small numbers throughout life. Small non-CR neurons differentiate first in the lower half of layer I, thereafter also in the upper half. Histochemically, all CR cells are AChE-positive; they contain NADPH-d only transiently at 20 GW. We propose that CR cells and SGL provide a transient innervation network for the developing cortical plate at a time when the definitive fiber systems of the molecular layer are not yet established.