Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos
Serotonin signaling is a very early step in patterning of the left-right axis in chick and frog embryos
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DOI：
10.1016/j.cub.2005.03.044
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发表时间：
2005-05-10
期刊：
影响因子：
9.2
通讯作者：
Levin, M
中科院分区：
文献类型：
--
作者：
Fukumoto, T;Kema, IP;Levin, M
背景：在发育和进化生物学中，持续的左右（LR）不对称是一个令人着迷的问题。在脊椎动物中，早期LR模式步骤的保护以及非蛋白小分子信使的参与非常不清楚。血清素（5-HT）是一种重要的神经递质，在生理和认知中起着至关重要的作用。我们验证了LR模式需要神经前5-羟色胺信号传导的假设，并表征了鸡和青蛙胚胎的5-羟色胺通路。结果：药理学筛选表明，内源性信号通过受体R3和R4以及单胺氧化酶（MAO）的活性参与了非洲爪蟾胚胎不对称基因表达和内脏的正确性建立。高效液相色谱和免疫组织化学分析表明，爪蟾卵含有母体供应的血清素，在卵裂阶段逐渐降解。血清素在青蛙胚胎中的动态定位需要间隙连接通讯和H， k - atp酶的功能。在右侧腹侧卵裂球中微量注射功能丧失和功能获得构建物随机化了不对称性。在鸡胚中，R3和R4活性位于Sonic hedgehog基因表达不对称性的上游。MAO在淋巴结中不对称表达。结论：血清素存在于很早的鸡和青蛙胚胎中。5-HT通路的功能是正常不对称所必需的，是不对称基因表达的上游。显微注射数据揭示了青蛙胚胎在4细胞阶段存在的不对称性，并提出了新的细胞内5-HT机制。这些功能和定位数据确定了神经递质5 -羟色胺的新作用，并暗示神经前5 -羟色胺能信号作为两种脊椎动物非常早期左右模式的必要方面。
Background: Consistent left-right (LR) asymmetry is a fascinating problem in developmental and evolutionary biology. Conservation of early LR patterning steps among vertebrates as well as involvement of nonprotein small-molecule messengers are very poorly understood. Serotonin (5-HT) is a key neurotransmitter with crucial roles in physiology and cognition. We tested the hypothesis that LR patterning required prenervous serotonin signaling and characterized the 5-HT pathway in chick and frog embryos.Results: A pharmacological screen implicated endogenous signaling through receptors R3 and R4 and the activity of monoamine oxidase (MAO) in the establishment of correct sidedness of asymmetric gene expression and of the viscera in Xenopus embryos. HPLC and immunohistochemistry analysis indicates that Xenopus eggs contain a maternal supply of serotonin that is progressively degraded during cleavage stages. Serotonin's dynamic localization in frog embryos requires gap junctional communication and H,K-ATPase function. Microinjection of loss- and gain-of-function constructs into the right ventral blastomere randomizes asymmetry. In chick embryos, R3 and R4 activity is upstream of the asymmetry of Sonic hedgehog expression. MAO is asymmetrically expressed in the node.Conclusions: Serotonin is present in very early chick and frog embryos. 5-HT pathway function is required for normal asymmetry and is upstream of asymmetric gene expression. The microinjection data reveal asymmetry existing in frog embryos by the 4-cell stage and suggest novel intracellular 5-HT mechanisms. These functional and localization data identify a novel role for the neurotransmitter serotonin and implicate prenervous serotonergic signaling as an obligate aspect of very early left-right patterning conserved to two vertebrate species.