Kinetics of proliferation and latency between final cell division and onset of differentiation of cerebellar stellate and basket neurons

Abstract

Thymidine‐3 autoradiographic, Golgi, and electonmicroscopic methods were combined to analyze proliferation kinetics and to determine the interval between final cell division and initial differentiation of interneurons of the cerebellar molecular layer (stellate and basket cells). The protracted span of development makes rhesus monkeys particularly suitable for unravelling temporal sequences in neurogenesis. Labeling index measurements in autoradiograms of adult animals injected at different developmental ages indicate that interneurons are generated at a steady rate of about 1% per day from the eightieth embryonic day to just after birth. The precursor pool is about 300,000 cells, each yielding on the average one differentiating and one proliferating daughter cell. The rate of interneuron proliferation parallels neither the exponential production of granule cells nor the 40‐fold expansion of cerebellar surface. Adult position of interneurons correlates with time of cell origin; the deep cells are generated first, the more superficial ones progressively later. By comparison of autoradiographic maps with Golgi impregnations and electronmicrographs at developmental stages, the interval from final mitosis to dendritic outgrowth and onset of synaptogenesis was found to increase systematically, reaching a maximum of two months for the last‐forming interneurons. Postmitotic interneurons, as yet without dendrites, accumulate at the interface between the external granular layer and the thickening molecular layer, and only later become enveloped by newly‐forming processes of other cells. Identified among these were mainly parallel fibers, some climbing fibers, axons of previously generated interneurons, and Purkinje dendrites. It is speculated that any or all of these may induce interneuron differentiation, since proliferation of any given interneuron is completed relatively early while it differentiates only later when its local milieu has developed.