Cell proliferation, migration and differentiation in the cerebral cortex of the golden hamster

Abstract

This work was undertaken: (1) to determine the sites of cell proliferation in the cerebral cortex of the hamster during prenatal life and shortly after birth; (2) to study the migration pattern of neuroblasts before and shortly after birth; and (3) to examine the differentiation of the neuroblasts during migration and after arrival at their final location. Tritiated thymidine was injected in pregnant hamsters at various days of gestation and in newborn animals. When one hour after treatment the parietal cortex of the embryos was examined for DNA synthesis, labeled cells were found in the neuroepithelial layer but not in the cortical layers. In the newborn radioactive cells were found both in the neuroepithelial layer and in the subependymal layer, a layer consisting of polymorph cells and developing at the end of prenatal life. Hence during embryonic life cell proliferation in the parietal cortex is restricted to the neuroepithelial layer, but in the newborn the subependymal layer is also ctive in cell production. When the generation time of the neuroepithelium was determined, the DNA synthetic phase was found to be six hours, the pre‐duplication and prophase about one and one‐half hours and the post‐duplication stage about four and one‐half hours. Hence the duration of the generation time of the neuroepithelial cells during embryonic life is about 12 hours. To examine the migration pattern of the neurons formed during embryonic and postnatal life, pregnant hamsters were injected at successive days of gestation and the embryos sacrificed at the twentieth postnatal day. A similar procedure was followed for newborn animals. It was thus found that neuroblasts formed during the early stages of development occupy the deep layers of the cortex, while those formed during the later stages of intrauterine life and during the first postnatal days occupy the more superficial layers. Hence, neuroblasts produced during the final stages of development migrate through the cell layers formed at previous days to reach the surface of the cortex. The time required for this migration varied in the newborn hamster from three to five days. When newborn hamsters were injected with tritiated thymidine and the labeled cells traced during the following ten days, it was noted that the cells released by the neuroepithelial layer arrived in the deeper layer of the cortex about 48 hours after labeling. The cells were characterized by a spindle‐shaped nucleus while the cytoplasm was seen to extend in peripheral direction. Shortly after arrival at the surface of the cortex the cells lost their spindle shape and the nucleus became oval‐shaped with a pale nucleoplasm. Subsequently the cells were characterized by a small round pale nucleus with two or three nucleoli close to the nuclear membrane. Approximately nine days after treatment the labeled cells were clearly recognizable as advanced neuroblasts with a large, pale nucleus and one or two nucleoli.