Cell Proliferation in the Developing Human Cerebral Cortex

Abstract

Cell proliferation or cell division has been considered a very important morphogenetic process during the development of the central nervous system. To determine the spatiotemporal pattern of proliferation in the developing human fetal brain, we used a specific antibody against the proliferation cell nuclear antigen (PCNA) and an immunohistochemical method to detect dividing cells in four neocortical regions, namely frontal, motor, occipital and temporal cortices, of human fetuses at different development stages (from 14 weeks to term). Positive cells were mostly found in the subcortical region of the neocortical regions at all the stages examined, although the developing cortical plate also occasionally showed scattered positive cells. Among the neocortical regions studied, the temporal cortex appeared to have the fewest positive cells, while the occipital cortex at 32 and 40 weeks contained the largest number of dividing cells. The PCNA immunoreactivity decreased rapidly with gestational age. The number of positive cells started to decrease early in the temporal cortex, from 14 weeks onwards, while in the motor and frontal cortices, a two-step decrease was seen between 14 and 21 weeks and between 27 and 32 weeks. In the occipital cortex, a decrease was also observed between 27 and 32 weeks, but only after an initial increase between 14 and 21 weeks. Our study thus clearly demonstrates specific patterns of regional as well as temporal distribution of dividing cells in the human fetal neocortex. Colocalization of PCNA with the glial fibrillary acidic protein and vimentin indicates that a majority of dividing cells are glial cells, especially toward late gestation.