Identification of a postnatal period of interdependent neurogenesis and apoptosis in peripheral neurons

Abstract

During neurogenesis, excessive numbers of neurons are produced in most regions of the central and peripheral nervous systems. Nonessential neurons are eliminated by apoptosis, or programmed cell death. This has been most thoroughly characterized in the peripheral nervous system (PNS) where targets of innervation play a key role in this process. As maturing neurons project axons towards their targets of innervation, they become dependent upon these targets for survival. Survival factors, also called neurotrophic factors, are produced by targets, inhibit apoptosis cascades, and promote further growth and differentiation. Because neurotrophic factors are limited, as is target size, neurons that do not correctly and efficiently innervate targets undergo apoptosis ( Levi-Montalcini, 1987; Davies, 1996). Thus, excessive neurogenesis acts to ensure that sufficient numbers of neurons are produced during development. In the superior cervical ganglion (SCG), this process of neurogenesis and subsequent apoptosis is reported to be complete by postnatal day 3-4 (P3-P4) in mice. Surprisingly, we observed significant numbers of apoptotic neurons out to P14, and neurogenesis was still present at P14 as well. In both the SCG and geniculate ganglion (GG), postnatal neurogenesis was dependent on apoptosis because little or no postnatal neurogenesis was observed in Bax-/- mice, in which apoptosis is eliminated. These results indicate that both neurogenesis and apoptosis continue to occur well after birth in peripheral ganglia, and that neurogenesis depends on apoptosis, suggesting that neurogenesis continues postnatally to replace neurons that are eliminated during synaptic refinement.