Heterogeneous requirement of NGF for sympathetic target innervation in vivo
Heterogeneous requirement of NGF for sympathetic target innervation in vivo
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DOI：
10.1523/jneurosci.4523-03.2004
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发表时间：
2004-01-21
影响因子：
5.3
通讯作者：
Ginty, DD
中科院分区：
文献类型：
--
作者：
Glebova, NO;Ginty, DD
神经营养因子神经生长因子（NGF）在交感神经系统的发育中起着至关重要的作用。除了在体内和体外交感神经元存活所必需的外，NGF已被证明在体外介导轴突生长。然而，由于其生存需要，神经生长因子在体内交感轴突生长中的作用尚不清楚。这一要求可以通过Bcl-2家族成员Bax的同时缺失来规避，从而可以独立于其在细胞存活中的功能来检查神经营养因子在轴突生长中的作用。在这里，我们分析了缺乏NGF和Bax的小鼠周围交感靶器官的神经支配。新生儿NGF(-/-)；在Bax（-/-）小鼠中，交感目标神经支配在某些器官（如唾液腺）中缺失，在其他器官（如心脏）中大大减少，在少数器官（如胃和肾脏）中有所减少，但在某些器官（如气管）中与对照组没有显著差异。在胚胎第16.5天，外周目标交感神经支配也在NGF中减少（-/-）；Bax（-/-）小鼠，不同器官具有类似的可变性。有趣的是，在一些器官如脾脏中，交感轴突依赖神经生长因子生长的精确位置是显而易见的。因此，我们表明，在体内，神经生长因子是椎旁和椎前交感神经节目标的完整周围神经支配所必需的，而不是细胞存活所需的。值得注意的是，靶器官对交感神经支配的NGF需求差异很大。
The neurotrophin nerve growth factor (NGF) plays a crucial role in the development of the sympathetic nervous system. In addition to being required for sympathetic neuron survival in vivo and in vitro, NGF has been shown to mediate axon growth in vitro. The role of NGF in sympathetic axon growth in vivo, however, is not clear because of its requirement for survival. This requirement can be circumvented by a concomitant deletion of Bax, a pro-apoptotic Bcl-2 family member, thus allowing an examination of the role of neurotrophins in axon growth independently of their function in cell survival. Here, we analyzed peripheral sympathetic target organ innervation in mice deficient for both NGF and Bax. In neonatal NGF(-/-); Bax(-/-) mice, sympathetic target innervation was absent in certain organs (such as salivary glands), greatly reduced in others (such as heart), somewhat diminished in a few (such as stomach and kidneys), but not significantly different from control in some (such as trachea). At embryonic day 16.5, peripheral target sympathetic innervation was also reduced in NGF(-/-); Bax(-/-) mice, with analogous variability for different organs. Interestingly, in some organs such as the spleen the precise location at which sympathetic axons become NGF-dependent for growth was evident. We thus show that NGF is required for complete peripheral innervation of both paravertebral and prevertebral sympathetic ganglia targets in vivo independently of its requirement for cell survival. Remarkably, target organs vary widely in their individual NGF requirements for sympathetic innervation.