Serotonin promotes Go-dependent neuronal migration in Caenorhabditis elegans
Serotonin promotes Go-dependent neuronal migration in Caenorhabditis elegans
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DOI：
10.1016/s0960-9822(02)01199-5
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发表时间：
2002-10-15
期刊：
影响因子：
9.2
通讯作者：
Schafer, WR
中科院分区：
文献类型：
--
作者：
Kindt, KS;Tam, T;Schafer, WR
背景：神经元在发育过程中的定向迁移需要控制迁移方向的吸引和排斥信号，以及增强细胞运动性和对引导分子的反应性的允许信号。结果：在这里，我们发现神经递质5 -羟色胺是线虫胚胎和胚胎后神经元迁移的许可信号。在血清素缺乏的突变体中，ALM、BDU、SDOR和AVM神经元的迁移经常被缩短或误导，表明正常迁移需要血清素。此外，外源性5 -羟色胺可以恢复血清素缺乏突变体AVM神经元的运动性，并诱导正常无运动神经元PVM的AVM样迁移；这表明5 -羟色胺作为一个允许的线索，使神经元运动。5 -羟色胺缺乏突变体的迁移缺陷通过5 -羟色胺能神经内分泌细胞的消融来模拟，暗示在这些过程中5 -羟色胺的体液释放。g和g信号缺陷或n型电压门控钙通道缺陷的突变体表现出与5 -羟色胺缺陷突变体相似的迁移表型，这些分子似乎在5 -羟色胺下游的遗传功能中控制神经元迁移。结论：因此，血清素在秀丽隐杆线虫神经系统发育过程中对促进定向神经元迁移具有重要作用。我们假设5 -羟色胺可能通过G蛋白依赖性调节迁移细胞中的电压门控钙通道来促进细胞运动。
Background: The directed migration of neurons during development requires attractive and repulsive cues that control the direction of migration as well as permissive cues that potentiate cell motility and responsiveness to guidance molecules.Results: Here, we show that the neurotransmitter serotonin functions as a permissive signal for embryonic and postembryonic neuronal migration in the nematode C. elegans. In serotonin-deficient mutants, the migrations of the ALM, BDU, SDOR, and AVM neurons were often foreshortened or misdirected, indicating a serotonin requirement for normal migration. Moreover, exogenous serotonin could restore motility to AVM neurons in serotonin-deficient mutants as well as induce AVM-like migrations in the normally nonmotile neuron PVM; this indicates that serotonin was functioning as a permissive cue to enable neuronal motility. The migration defects of serotonin-deficient mutants were mimicked by ablations of serotonergic neuroendocrine cells, implicating humoral release of serotonin in these processes. Mutants defective in G. and G. signaling, or in N-type voltage-gated calcium channels, showed migration phenotypes similar to serotonin-deficient mutants, and these molecules appeared to genetically function downstream of serotonin in the control of neuronal migration.Conclusions: Thus, serotonin is important for promoting directed neuronal migration in the developing C. elegans nervous system. We hypothesize that serotonin may promote cell motility through G protein-dependent modulation of voltage-gated calcium channels in the migrating cell.