Cell proliferation and migration in the primitive ependymal zone: an autoradiographic study of histogenesis in the nervous system.

Thymidine was incorporated into deoxyribonucleic acid (DNA) of cells preparing for division. Autoradiography with tritium-labeled thymidine (thymidine-H3) provided a method of marking such cells in the reletively inaccessible mammalian embryo. Pregnant mice were injected intravenously with thymidine-H3 and killed at various intervals. Autoradiograms were prepared of sections through the embryonic brains. Eleven-day embryos fixed 1 hour after exposure to thymidine-H3 showed heavy labeling of most cell nuclei in the external half of the primitive ependymal layer in the wall of the cerebral vesicle, and almost no labeling in the inner half. Thus, the external half of the primitive ependymal layer is the site of DNA synthesis. Six hours after exposure to thymidine-H3, the labeled nuclei occupied the inner (ventricular) half of the primitive ependymal layer, and most mitotic figures at the ventricular surface contained labeled chromosomes. Forty-eight hours after injection, labeled nuclei had migrated laterally; some had entered the developing mantle layer, but many remained in the primitive ependyma and had repeated the cycle of DNA synthesis, migration, and division. Development of the primitive ependyma was similar throughout the embryonic nervous system. The data show that the cells of the primitive ependymal layer behave synchronously, and that the sites of DNA synthesis and mitosis are different. The views of Schaper and Sauer are confirmed: the primitive ependymal layer is a pseudostratified columnar epithelium within which nuclei of undifferentiated cells migrate to and fro in relation to the mitotic cycle.