Kindt Katie S, Tam Tobey, Whiteman Shaleah, Schafer William R
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0349, USA.
Curr Biol. 2002 Oct 15;12(20):1738-47. doi: 10.1016/s0960-9822(02)01199-5.
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.
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, SDQR, 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(q) and G(o) 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.
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.
神经元在发育过程中的定向迁移需要吸引和排斥信号来控制迁移方向，以及允许信号来增强细胞运动性和对导向分子的反应性。
在此，我们表明神经递质5-羟色胺在秀丽隐杆线虫胚胎期和胚胎后期神经元迁移中作为一种允许信号发挥作用。在5-羟色胺缺陷型突变体中，ALM、BDU、SDQR和AVM神经元的迁移常常缩短或方向错误，这表明正常迁移需要5-羟色胺。此外，外源性5-羟色胺可恢复5-羟色胺缺陷型突变体中AVM神经元的运动性，并在正常情况下不运动的PVM神经元中诱导出类似AVM的迁移；这表明5-羟色胺作为一种允许信号来促进神经元运动。5-羟色胺能神经内分泌细胞的消融模拟了5-羟色胺缺陷型突变体的迁移缺陷，这意味着这些过程中5-羟色胺的体液释放。G(q)和G(o)信号传导缺陷或N型电压门控钙通道缺陷的突变体表现出与5-羟色胺缺陷型突变体相似的迁移表型，并且这些分子在控制神经元迁移中似乎在5-羟色胺的遗传下游发挥作用。
因此，5-羟色胺对于促进秀丽隐杆线虫发育中的神经系统中神经元的定向迁移很重要。我们推测5-羟色胺可能通过对迁移细胞中电压门控钙通道的G蛋白依赖性调节来促进细胞运动。
