Prenatal development of the cerebellar system in the rat. I. Cytogenesis and histogenesis of the deep nuclei and the cortex of the cerebellum

Abstract Prenatal cerebellar development was investigated with three approaches. In normal embryos sectioned in three planes morphological and cytological changes were determined at daily intervals beginning on embryonic day 13 (E13). A similar series of X‐irradiated embryos was used to study changes in neuroepithelial organization and in the location of primitive (radiosensitive) or differentiated cells. Finally, to quantify the time of origin of different classes of cerebellar neurons with the progressively delayed labelling procedure, we used autoradiograms from adult rats whose mothers were injected with two successive daily doses of 3 H‐thymidine on overlapping days from day E13 on. The cerebellar anlage was delineated in the dorsal metencephalon by the collapse of its ventricular lining after X‐irradiation. This “collapsing neuroepithelium” was located laterally on day E13, then it spread medially and reached the midline on day E16. Deep nuclear neurons began to differentiate on day E13, with two‐thirds forming on day E14; Purkinje cell formation peaked on day E15, with a few cells still forming on day E16. It was postulated that the deep nuclear neurons settled first in the superficial “nuclear zone,” and that the Purkinje cells gathered temporarily in the underlying “transitory zone,” adjacent to the collapsing neuroepithelium. In the next period of cerebellar development four major events were recognized. (1) Beginning on day E17 the cells of the nuclear and transitory zones became intermingled. It was postulated that the Purkinje cells were migrating radially through the ranks of the stationary deep nuclear neurons and assembled under the spreading canopy of a fibrous plexus and the external germinal layer. (2) It was also on day E17 that the external germinal layer began to form as one of the prongs of the “germinal trigone” in the posteroventral aspect of the cerebellum. On the succeeding days the external germinal layer spread over the surface of the cerebellum; in the vermis in a rostral direction. (3) Two cell types destined to settle in the future granular layer, the pale cells and the Golgi cells, began to form at a relatively slow rate on day E19. Chronological considerations suggested that they were generated in the regressing, noncollapsing neuroepithelium of the cerebellar ventricle. (4) From the beginning (day E17) of its genesis posteroventrally, the primitive cerebellar cortex bridged the midline. As the fused cortex spread rostrally, the vertical ventricular cleft separating the underlying portions of the cerebellum became shallower and then disappeared; the process was completed in the anterior cerebellum by day E22. By the time of birth the maturation of the neurons of the deep nuclei appeared advanced but the maturation of the prenatally produced neurons of the cortex does not start until after birth when a new class of neurons is generated in the external germinal layer.