Misplacement of Purkinje cells during postnatal development in Bax knock-out mice: a novel role for programmed cell death in the nervous system?

Abstract

During early postnatal development, the orchestrated regulation of proliferation, migration and the survival versus elimination of neurons is essential for histogenesis of the cerebellum. For instance, Purkinje cells (PCs) promote the proliferation and migration of external granule cells (EGCs), whereas EGCs in turn play a role in the migration of PCs. Considering that a substantial number of neurons undergo programmed cell death (PCD) during cerebellar development, it seems likely that neuronal loss could have a significant role in the histogenesis of the cerebellum. To address this question, we examined postnatal development of the cerebellum in Bax-knock-out (KO) mice in which the PCD of PC has been reported to be selectively reduced or eliminated, whereas EGCs are unaffected. We confirmed the absence of PC PCD as well as the normal PCD of EGCs in Bax-KO mice. We also observed a subpopulation of PCs that were misplaced in the inner granule cell layer of Bax-KO mice on postnatal day 5 (P5) to P10 and that, by the end of the major period of cerebellar histogenesis (P14), lose expression of the PC marker calbindin. These results suggest that the removal of ectopically located neurons may be a previously unrecognized function of developmental PCD.