Programmed cell death in zebrafish Rohon Beard neurons is influenced by TrkC1/NT-3 signaling

Rohon Beard (RB) cells are embryonic primary sensory neurons that are removed by programmed cell death during larval development in zebrafish. RE somatosensory functions are taken over by neurons of the dorsal root ganglia (DRG), suggesting that RE cell death may be triggered by the differentiation of these ganglia, as has been proposed to be the case in Xenopus. However, here we show that the timing of RE cell death correlates with reduced expression of trkC1, the receptor for neurotrophin NT-3, but not with the appearance of DRG, which differentiate only after most RE cells die. trkC1 is expressed in subpopulations of RE neurons during development, and cell death is initiated only in trkC1-negative neurons, suggesting a role for TrkC1 and its ligand, NT-3, in RE cell survival. In support of this, antibodies that deplete NT-3 induce RE cell death while exogenous application of NT-3 reduces death. In addition, we show that RE cell death can be prevented using a caspase inhibitor, zVADfmk, showing that during normal development, RE cells die by a caspase-dependent programmed cell death pathway possibly triggered by reduced signaling via TrkC1. (C) 2000 Academic Press.