Williams J A, Barrios A, Gatchalian C, Rubin L, Wilson S W, Holder N
Department of Anatomy and Developmental Biology, University College of London, London, United Kingdom.
Dev Biol. 2000 Oct 15;226(2):220-30. doi: 10.1006/dbio.2000.9860.
Rohon Beard (RB) cells are embryonic primary sensory neurons that are removed by programmed cell death during larval development in zebrafish. RB somatosensory functions are taken over by neurons of the dorsal root ganglia (DRG), suggesting that RB 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 RB 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 RB cells die. trkC1 is expressed in subpopulations of RB neurons during development, and cell death is initiated only in trkC1-negative neurons, suggesting a role for TrkC1 and its ligand, NT-3, in RB cell survival. In support of this, antibodies that deplete NT-3 induce RB cell death while exogenous application of NT-3 reduces death. In addition, we show that RB cell death can be prevented using a caspase inhibitor, zVADfmk, showing that during normal development, RB cells die by a caspase-dependent programmed cell death pathway possibly triggered by reduced signaling via TrkC1.
罗霍恩·比尔（RB）细胞是胚胎期的初级感觉神经元，在斑马鱼幼体发育过程中会通过程序性细胞死亡被清除。RB的躯体感觉功能由背根神经节（DRG）的神经元接管，这表明RB细胞死亡可能是由这些神经节的分化触发的，就像在非洲爪蟾中所提出的情况那样。然而，我们在此表明，RB细胞死亡的时间与神经营养因子NT - 3的受体trkC1表达的降低相关，而与DRG的出现无关，DRG是在大多数RB细胞死亡后才分化的。trkC1在发育过程中在RB神经元的亚群中表达，并且细胞死亡仅在trkC1阴性的神经元中启动，这表明TrkC1及其配体NT - 3在RB细胞存活中起作用。支持这一点的是，消耗NT - 3的抗体诱导RB细胞死亡，而外源性应用NT - 3则减少死亡。此外，我们表明使用半胱天冬酶抑制剂zVADfmk可以防止RB细胞死亡，这表明在正常发育过程中，RB细胞通过可能由经由TrkC1的信号传导减少触发的半胱天冬酶依赖性程序性细胞死亡途径死亡。
