Immunohistochemical identification of some plasma proteins in human embryonic and fetal forebrain with particular reference to the development of the neocortex.

The histogenesis of the cerebral neocortex has been studied in human embryos and fetuses from the ventricular zone stage at 9-10 mm crown-rump length (CRL) to the well-developed neocortex at 210 mm CRL. The initial proliferation of the neuroepithelial cells in the ventricular zone stage was followed by a stage characterized by a ventricular zone covered by a primordial plexiform layer; the subventricular zone then arose before the cortical plate was formed within the primordial plexiform layer, thus dividing it into an outer marginal zone and an inner subplate zone; finally the intermediate zone appeared between the subventricular and subplate zones. The distribution of cells containing albumin, alpha-fetoprotein, transferrin, prealbumin, IgG and alpha 1-antitrypsin in the cerebral vesicle and developing neocortex was investigated by the indirect immunoperoxidase technique. Alpha-fetoprotein found in the cells of the ventricular zone was the most widespread and prominent of the plasma proteins examined in the early embryos. The cerebral vesicle was negative for all other plasma proteins investigated at this stage. By 15 and 16 mm CRL, a few cells in the ventricular zone were positive for albumin and transferrin whereas AFP exhibited a distribution similar to that of the 9 mm embryo. By 20-25 mm CRL, albumin and AFP had a similar distribution in the telencephalic wall. At 40-150 mm CRL a positive staining reaction for AFP, albumin, prealbumin and transferrin was predominant in the outer half of cortical plate. At 150-170 mm CRL only cells in the inner half exhibited positive staining and at 210 mm CRL the staining reactions were negative. The cells containing plasma proteins did not belong to a single cell line or type; thus plasma proteins were detected primarily in different types of neurons but also in glial cells. Staining with polyvalent antiserum indicated that the same cells may be positive for more than one plasma protein. Positive staining reactions were also observed in or along fiber systems. It is proposed that cells initially take up plasma protein from the CSF and migrate with it towards the cortical plate. After a certain period they lose their plasma protein but when the neuronal cells which represent the majority of the positively stained cells have reached their final position in the cortical plate they commence plasma protein synthesis which continues for a short period during which the neurons establish their pattern of connectivity.