Histogenesis of cortical layers in human cerebellum, particularly the lamina dissecans

Patterns of lamination during development of the fetal human cerebellar cortex were analyzed in Nissl- and H & E-stained serial sections, rapid Golgi preparations, reduced silver impregnations, electron micrographs, and autoradiograms. The layering pattern changed dramatically with time, as analyzed in detail for the culmen, the earliest region to differentiate. Up to about 10 weeks of gestation, cells proliferated only at or near the ventricular surface and migrated radially outward to occupy the full thickness of the cerebellar primordium except for an outermost cell-sparse marginal layer (2-layer stage). The external granular layer first appeared at 10-11 weeks while another group of cells became concentrated beneath the marginal layer (3-layer stage). At 20–21 weeks the lamina dissecans first became evident as a relatively acellular band in the midst of the zone of compact cells below the marginal (now molecular) layer, and for the next ten weeks the cerebellar cortex displayed this 5-layered form. At about 32 weeks the lamina dissecans disappeared (4-layer stage) and postnatally the external granular layer in turn disappeared as the last of its cells migrated inward (adult 3-layer configuration). The Purkinje cell population was established by 13 weeks, though the cerebellum was destined subsequently to increase several orders of magnitude in surface area and volume. The increase was achieved in part by cell growth, but mainly by extensive cell proliferation in the external granular layer. At 22 weeks, about 30% of the external granular cells incorporated thymidine-H3 upon a single supravital exposure; the external granular layer attained maximum cell number at some stage after birth. At the 5-layer stage from about 21 to 32 weeks, the interrelationships between various classes of young neurons in the cerebellar cortex became very complex. The Purkinje cells developed ascending branched dendritic processes with growth cones and displayed transient short cytoplasmic processes that extended from the soma in all derections. Basket cell neurons had formed but their axons appeared not to envelop the Purkinje somas as yet. Less mature, smaller cells were beginning to migrate from the external granular layer inward past the Purkinje somas. Their cell bodies in the newly forming granular were separated from the Purkinje cell bodies by a dense tangle of axons in the lamina dissecans. Many of these axons terminated in swellings interpreted tentatively as immature mossy endings, while others passed outward to enclose the cell bodies and proximal dendrites of the Purkinje cells. Some general points emerged from a comparison of cerebellar development in man and animals. The time of cell origin cannot be inferred necessarily from the time of overt differentiation; deep cerebellar neurons and Purkinje neurons arise in the first trimester, but the former cells differentiate much earlier. Purkinje cells acquired characteristic shapes by the middle of gestation, when very few granule cell neurons had yet formed, and thus appear to develop relatively independently of the granule cells. Although the adult cerebellum appears to be organized similarly among mammals, a developmental component, the lamina dissecans, has been illustrated only in man and whale; its appearance may reflect the combination of early Purkinje cell and late granule cell differentiation in species with a prolonged period of development. One of the most intriguing features of the lamina dissecans is that it appears to contain axon terminals at a time prior to the arrival of the postsynaptic cells.