Wetts R, Vaughn J E
Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
J Neurosci. 1998 Sep 1;18(17):6905-13. doi: 10.1523/JNEUROSCI.18-17-06905.1998.
Developmental cell death in the nervous system usually is controlled by the availability of target-derived trophic factors. It is well established that dorsal root ganglia (DRG) neurons require the presence of their peripheral target for survival, but because of their central projections, it is possible that the spinal cord also may be required. Before examining this possibility in rat embryos, we first used terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) to determine that thoracic DRG cell death occurred from embryonic day 15 (E15) to E18. To determine the target requirements of DRG neurons, we used organotypic slice cultures of E15 thoracic trunk segments. After peripheral target removal, essentially all DRG neurons disappeared within 5 d. In contrast, after removal of the spinal cord, approximately half of the DRG neurons survived for at least 8 d. Hence, some E15 DRG neurons could survive without the spinal cord. However, those DRG neurons that died after spinal cord ablation apparently required trophic factors from both central and peripheral targets, because the presence of only one of these tissues was not adequate by itself to support this cell group. Addition of neurotrophin-3 (NT-3) to the culture medium rescued some DRG neurons after CNS removal, suggesting a possible role for NT-3 in vivo. In other experiments, cultures were established from older (E16) embryos, and essentially all neurons survived after spinal cord ablation, even without added factors. These and other experiments indicated that approximately 65% of DRG neurons are transiently dependent on the CNS early in development.
神经系统中的发育性细胞死亡通常受靶源性营养因子可用性的控制。背根神经节（DRG）神经元需要其外周靶标的存在才能存活，这一点已得到充分证实，但由于其具有向中枢的投射，脊髓也可能是必需的。在对大鼠胚胎进行这一可能性研究之前，我们首先使用末端脱氧核苷酸转移酶介导的生物素化UTP缺口末端标记法（TUNEL）确定胸段DRG细胞死亡发生在胚胎第15天（E15）至E18天。为了确定DRG神经元对靶标的需求，我们使用了E15胸段躯干节段的器官型切片培养。去除外周靶标后，基本上所有的DRG神经元在5天内消失。相比之下，去除脊髓后，大约一半的DRG神经元存活了至少8天。因此，一些E15 DRG神经元在没有脊髓的情况下也能存活。然而，那些在脊髓切除后死亡的DRG神经元显然需要来自中枢和外周靶标的营养因子，因为仅其中一个组织的存在本身不足以支持这个细胞群。在培养基中添加神经营养素-3（NT-3）可在去除中枢神经系统后挽救一些DRG神经元，这表明NT-3在体内可能发挥作用。在其他实验中，从较老（E16）的胚胎建立培养，即使不添加因子，脊髓切除后基本上所有神经元都能存活。这些及其他实验表明，大约65%的DRG神经元在发育早期短暂依赖中枢神经系统。
