Cell death as a regulator of cerebellar histogenesis and compartmentation.

Programmed cell death is essential for the homeostasis of tissues and organs. During the development of the central nervous system, programmed cell death is highly regulated and restricted to distinct developmental time points of histogenesis. In this review, we will summarize recent data on the temporal and spatial distribution of programmed Purkinje cell death within the cerebellar cortex. We point out that programmed cell death within distinct regions of the developing cerebellar cortex differs by type and its cellular consequences. We submit the concept that local Purkinje cell death is important for late compartmentation of the cerebellar cortex and its wiring. To support this hypothesis, we provide new data obtained from a cerebellar mutant with prolonged expression of Engrailed-2 specifically in cerebellar Purkinje cells which shows increased local physiological cell death and concomitant changes in the pattern of afferent innervation.