The role of GDNF family ligand signalling in the differentiation of sympathetic and dorsal root ganglion neurons.
The role of GDNF family ligand signalling in the differentiation of sympathetic and dorsal root ganglion neurons.
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DOI：
10.1007/s00441-008-0634-4
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发表时间：
2008-09
影响因子：
3.6
通讯作者：
Ernsberger, Uwe
中科院分区：
文献类型：
--
作者：
Ernsberger, Uwe
交感神经节和背根神经节（DRG）中神经元的多样性为神经元分化的分析提供了有趣的系统。 GDNF 家族配体 (GFL)、神经胶质细胞源性神经营养因子 (GDNF)、neurturin 和 artemin 的细胞表面受体在这些神经元亚群中表达，引发了关于它们参与神经元亚型规范的问题。小鼠突变分析表明，胆碱能交感神经元胚胎发育过程中需要 GFL 信号传导，如缺乏 ret（GFL 受体复合物的信号转导亚基）的小鼠神经节中胆碱能基因座表达的丧失即可证明。对过表达 GFL 的突变动物和转基因小鼠的分析表明，DRG 神经元对热和机械刺激的敏感性有影响，至少部分与瞬时受体电位离子通道和酸敏感阳离子通道的表达改变相关。突变神经节中靶细胞的持续存在表明这些改变是由分化效应引起的，而不是由细胞损失引起的。由于 GFL 对神经突生长的巨大影响，GFL 信号是否直接作用于神经元规范，或通过改变靶神经支配和获取其他生长因子间接作用，仍有待确定。数据表明，感觉神经元和自主神经元亚群的规范需要 GFL 信号传导。为了充分理解这一过程，需要破译单个 GFL 的作用、GFL 信号的转导以及 GFL 信号传导与其他调节途径的相互作用。
The diversity of neurons in sympathetic ganglia and dorsal root ganglia (DRG) provides intriguing systems for the analysis of neuronal differentiation. Cell surface receptors for the GDNF family ligands (GFLs) glial cell-line-derived neurotrophic factor (GDNF), neurturin and artemin, are expressed in subpopulations of these neurons prompting the question regarding their involvement in neuronal subtype specification. Mutational analysis in mice has demonstrated the requirement for GFL signalling during embryonic development of cholinergic sympathetic neurons as shown by the loss of expression from the cholinergic gene locus in ganglia from mice deficient for ret, the signal transducing subunit of the GFL receptor complex. Analysis in mutant animals and transgenic mice overexpressing GFLs demonstrates an effect on sensitivity to thermal and mechanical stimuli in DRG neurons correlating at least partially with the altered expression of transient receptor potential ion channels and acid-sensitive cation channels. Persistence of targeted cells in mutant ganglia suggests that the alterations are caused by differentiation effects and not by cell loss. Because of the massive effect of GFLs on neurite outgrowth, it remains to be determined whether GFL signalling acts directly on neuronal specification or indirectly via altered target innervation and access to other growth factors. The data show that GFL signalling is required for the specification of subpopulations of sensory and autonomic neurons. In order to comprehend this process fully, the role of individual GFLs, the transduction of the GFL signals, and the interplay of GFL signalling with other regulatory pathways need to be deciphered.
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