Dorsal root ganglion cell death and surviving cell numbers in relation to the development of sensory innervation in the rat hindlimb.

This study correlates the numbers of dying, surviving and proliferating L4 primary afferent neurons with the development of peripheral hindlimb sensory innervation in the rat. Cell death occurs from embryonic day 15 (E15) to just after birth and peaks at E17-E19. Despite this, surviving cell numbers rise steadily to birth indicating that cell death is more than balanced by cell proliferation over this period. GAP-43 immunostaining indicates that the peripheral sensory axons are only in central parts of the hindlimb by E15 and do not finish arriving at their distal peripheral targets until birth so prenatal cell death in the L4 ganglion is not well correlated with the development of the peripheral innervation by these primary sensory axons. Prenatal cell death does, however, correlate well with the innervation of the cord by central sensory axons. In contrast to the steady rise of surviving cell numbers from E15 to birth, cell numbers go down 16% in the period from birth to postnatal day 5. This loss is correlated with the development of the peripheral innervation. We conclude that the bulk of cell death in the rat L4 dorsal root ganglion, which is prenatal, is controlled by local or central factors whereas peripheral target factors may exert their influence postnatally to determine the final numbers of mammalian sensory neurons. The data also suggest that there may be two phases of cell death, an early phase involving large light cells and a late phase involving small dark cells.