Gagliardini V, Fankhauser C
Department of Neuromorphology, Brain Research Institute, University of Zurich and Swiss Federal Institute of Technology Zurich.
Mol Cell Neurosci. 1999 Oct-Nov;14(4-5):301-16. doi: 10.1006/mcne.1999.0787.
Semaphorin III has been described to function as a guidance molecule directing growing axons to their target. However, its effect on the neuron cell body has not been characterized. Semaphorin III has a highly dynamic expression pattern, which generally corroborates a chemorepellent guidance function, but also suggests additional functions, different from axon guidance. A number of studies show that some sensory neurons are eliminated, while their axons are still pathfinding. In this study we have investigated whether Semaphorin III also influences the survival of sensory neurons. We here present evidence that Semaphorin III can function in vitro as selective death factor for NGF-dependent sensory neurons. Semaphorin III induces a type of cell death that is characterized by slow onset, cell body shrinking, nuclear condensation, and TUNEL-positive staining of dying neurons. These are all hallmarks of neuronal apoptosis. We also show evidence that neurons can modulate the response to Semaphorin III. The novel function described here may also be relevant in vivo, contributing to active elimination of neurons during development or after injury.
信号素III已被描述为一种引导分子，可引导生长中的轴突到达其靶标。然而，它对神经元细胞体的影响尚未得到明确描述。信号素III具有高度动态的表达模式，这通常证实了其化学排斥引导功能，但也暗示了与轴突引导不同的其他功能。一些研究表明，一些感觉神经元在其轴突仍在寻找路径时就被消除了。在本研究中，我们调查了信号素III是否也影响感觉神经元的存活。我们在此提供证据表明，信号素III在体外可作为NGF依赖型感觉神经元的选择性死亡因子。信号素III诱导一种细胞死亡，其特征为起效缓慢、细胞体萎缩、核浓缩以及死亡神经元的TUNEL阳性染色。这些都是神经元凋亡的标志。我们还表明，神经元可以调节对信号素III的反应。这里描述的新功能在体内可能也很重要，有助于在发育过程中或损伤后主动消除神经元。
