Early development and composition of the human primordial plexiform layer: An immunohistochemical study

The early expression of reelin, calcium-binding proteins (calretinin, calbindin, and parvalbumin), and neurofilament proteins have been explored in the developing central nervous system of human embryos and fetuses during the first trimester of gestation. Our objective has been to determine further the nature, developmental roles, and contributions of the early neurons and fibers of the original subpial neuropil, i.e., the primordial plexiform layer (PPL). In young embryos (4-5 weeks old), neurofilament protein-labeled fibers run through the subpial neuropil of the caudal portion of the neural tube, reaching the mesencephalon rostrally. At this age, calretinin-immunoreactive and calbindin-immunoreactive neurons are also found among cells already detached from the ventricular zone. The expression of neurofilament protein, calretinin, and calbindin follows an ascending caudorostral gradient, reaching the cerebral vesicles by the 6th-7th week of gestation. In the cerebral cortex, this timing coincides with the initial expression of reelin in the PPL. The reelin immunoreactivity throughout the most superficial cellular population of the cortical PPL supports the early genesis of Cajal-Retzius cells, around the 6th week of gestation. After the splitting of the PPL by the formation of the cortical plate (7-8 weeks of gestation), reelin-immunoreactive cells remain only in the newly established layer I. This study proposes that an initial PPL may be a universal feature of the developing central nervous system.