University of Hohenheim, Institute of Zoology, Garbenstrasse 30, D-70593 Stuttgart, Germany.
Differentiation. 2012 Feb;83(2):S67-77. doi: 10.1016/j.diff.2011.11.005. Epub 2011 Dec 1.
In vertebrates, laterality - the asymmetric placement of the viscera including organs of the gastrointestinal system, heart and lungs - is under the genetic control of a conserved signaling pathway in the left lateral plate mesoderm (LPM). A key feature of this pathway, shared by embryos of all non-avian vertebrate classes analyzed to date (e.g. fish, amphibia and mammals) is the formation of a transitory midline epithelial structure. Remarkably, the motility of cilia projecting from this epithelium produce a leftward-directed movement of extracellular liquid. This leftward flow precedes any sign of asymmetry in gene expression. Numerous analyses have shown that this leftward flow is not only necessary, but indeed sufficient to direct laterality. Interestingly, however, cilia-independent mechanisms acting much earlier in development in the frog Xenopus have been reported during the earliest cleavage stages, a period before any major zygotic gene transcription. The relationship between these two distinct mechanisms is not understood. In this review we present the conserved and critical steps of Xenopus LR axis formation. Next, we address the basic question of how an early asymmetric activity might contribute to, feed into, or regulate the conserved cilia-dependent pathway. Finally, we discuss the possibility that Spemann's organizer is itself polarized in the left-right dimension. In attempting to reconcile the sufficiency of the cilia-dependent pathway with potential earlier-acting asymmetries, we offer a general practical experimental checklist for the Xenopus community working on the process of left-right determination. This approach indicates areas where work still needs to be done to clarify the relationship between early determinants and cilia-driven leftward flow.
在脊椎动物中，内脏的不对称排列，包括胃肠道系统、心脏和肺部的器官，受左侧侧板中胚层（LPM）中保守信号通路的遗传控制。该途径的一个关键特征是，迄今为止分析的所有非鸟类脊椎动物类群（例如鱼类、两栖类和哺乳动物）的胚胎中都存在一种暂时性的中线上皮结构。值得注意的是，从中胚层上皮细胞伸出的纤毛的运动产生了一种向外的液体流动。这种向左的流动先于任何基因表达不对称的迹象。大量分析表明，这种向左的流动不仅是必要的，而且实际上足以指导不对称性。有趣的是，然而，在青蛙 Xenopus 的发育早期，即在任何主要的合子基因转录之前的最早分裂阶段，已经报道了纤毛独立的机制，其作用比这更早。这两种不同机制之间的关系尚不清楚。在这篇综述中，我们介绍了 Xenopus LR 轴形成的保守和关键步骤。接下来，我们解决了一个基本问题，即早期的不对称活动如何有助于、输入或调节保守的纤毛依赖途径。最后，我们讨论了 Spemann 组织者本身在左右维度上极化的可能性。在试图使纤毛依赖途径的充分性与潜在的早期作用的不对称性相协调时，我们为研究左右决定过程的 Xenopus 社区提供了一个一般性的实用实验清单。这种方法表明，在澄清早期决定因素与纤毛驱动的向左流动之间的关系方面，仍有工作需要做。
