D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.
D1-type dopamine receptors inhibit growth cone motility in cultured retina neurons: evidence that neurotransmitters act as morphogenic growth regulators in the developing central nervous system.
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DOI：
10.1073/pnas.85.8.2839
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发表时间：
1988-06
影响因子：
11.1
通讯作者：
K. Lankford;F. G. Demello;W. Klein
中科院分区：
文献类型：
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作者：
K. Lankford;F. G. Demello;W. Klein
脊椎动物中枢神经系统中神经递质受体系统的早期发育和随后的下调有先例，但这种胚胎受体的功能尚未确定。在这里，我们表明，刺激早期发展的多巴胺受体在鸟类视网膜细胞大大抑制神经生长锥的运动。将鸡胚视网膜神经元进行低密度单层培养，用相差显微镜或视频增强对比微分干涉对比（VEC-DIC）显微镜观察其生长锥。大约25%的神经元对微摩尔多巴胺产生反应，丝状伪足活动迅速减少，随后生长锥变平，神经突退缩。反应发生在所有年龄的检查（胚胎第8天的视网膜神经元培养的聚赖氨酸涂层盖玻片1-7天），虽然神经突收缩是最大的年轻文化。氟哌啶醇或（+）-SCH 23390可逆转多巴胺对生长锥功能的影响，而毛喉素引起的反应与多巴胺相似;这些数据表明该反应是受体介导的，通过D1型系统起作用，与cAMP作为第二信使的使用一致。这些实验提供了强有力的支持的假设，神经递质，除了介导跨突触信号在成人，可能有一个神经元分化的生长调节剂的作用。
Precedent exists for the early development and subsequent down-regulation of neurotransmitter receptor systems in the vertebrate central nervous system, but the function of such embryonic receptors has not been established. Here we show that stimulation of early-developing dopamine receptors in avian retina cells greatly inhibits the motility of neuronal growth cones. Neurons from embryonic chicken retinas were cultured in low-density monolayers, and their growth cones were observed with phase-contrast or video-enhanced-contrast-differential-interference-contrast (VEC-DIC) microscopy. Approximately 25% of the neurons responded to micromolar dopamine with a rapid reduction in filopodial activity followed by a flattening of growth cones and retraction of neurites. The response occurred at all ages examined (embryonic day-8 retinal neurons cultured on polylysine-coated coverslips for 1-7 days), although neurite retraction was greatest in younger cultures. Effects of dopamine on growth cone function could be reversed by haloperidol or (+)-SCH 23390, whereas forskolin elicited a response similar to dopamine; these data show the response was receptor-mediated, acting through a D1-type system, and are consistent with the use of cAMP as a second messenger. The experiments provide strong support for the hypothesis that neurotransmitters, besides mediating transynaptic signaling in the adult, may have a role in neuronal differentiation as growth regulators.