Serotonin has early, cilia-independent roles in Xenopus left-right patterning.

Serotonin has early, cilia-independent roles in Xenopus left-right patterning.
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DOI:
10.1242/dmm.010256
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发表时间:
2013-01
影响因子:
4.3
通讯作者:
Levin M
Levin M
中科院分区:
医学2区
文献类型:
--
作者:
Vandenberg LN;Lemire JM;Levin M

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心脏和内脏一致的左右(LR)模式是正常胚胎发生的关键部分。因为偏侧性错误形成了一类常见的出生缺陷,所以了解LR不对称的分子机制和阶段是很重要的。青蛙胚胎是一个独特的适合于分析与LR轴定位有关的机制的系统,因为有许多可供使用的遗传和药理学工具,以及早期卵裂球的命运图和可及性。LR不对称的起源有两种主要模式,两种模式都与神经前5-羟色胺能信号有关。在第一种情况下,带电的5-羟色胺分子对LR构型有指导作用;它沿着LR轴不对称地重新分布,并在分裂阶段在右侧细胞内发出信号。第二个模型表明,5-羟色胺是指定胚胎背部区域所需的一种允许因素,该区域含有手性纤毛,在神经形成期间产生不对称的液体流动,这是一个更晚的过程。我们进行了理论中立的实验,旨在区分这些模型。这些结果一致支持5-羟色胺在卵裂期胚胎中的作用,早在纤毛出现之前,在不对纤毛器官起作用的腹侧右卵裂球中。
Consistent left-right (LR) patterning of the heart and viscera is a crucial part of normal embryogenesis. Because errors of laterality form a common class of birth defects, it is important to understand the molecular mechanisms and stage at which LR asymmetry is initiated. Frog embryos are a system uniquely suited to analysis of the mechanisms involved in orientation of the LR axis because of the many genetic and pharmacological tools available for use and the fate-map and accessibility of early blastomeres. Two major models exist for the origin of LR asymmetry and both implicate pre-nervous serotonergic signaling. In the first, the charged serotonin molecule is instructive for LR patterning; it is redistributed asymmetrically along the LR axis and signals intracellularly on the right side at cleavage stages. A second model suggests that serotonin is a permissive factor required to specify the dorsal region of the embryo containing chiral cilia that generate asymmetric fluid flow during neurulation, a much later process. We performed theory-neutral experiments designed to distinguish between these models. The results uniformly support a role for serotonin in the cleavage-stage embryo, long before the appearance of cilia, in ventral right blastomeres that do not contribute to the ciliated organ.
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