Schweickert Axel, Ott Tim, Kurz Sabrina, Tingler Melanie, Maerker Markus, Fuhl Franziska, Blum Martin
Institute of Zoology, University of Hohenheim, 70593 Stuttgart, Germany.
J Cardiovasc Dev Dis. 2017 Dec 29;5(1):1. doi: 10.3390/jcdd5010001.
Laterality of inner organs is a wide-spread characteristic of vertebrates and beyond. It is ultimately controlled by the left-asymmetric activation of the Nodal signaling cascade in the lateral plate mesoderm of the neurula stage embryo, which results from a cilia-driven leftward flow of extracellular fluids at the left-right organizer. This scenario is widely accepted for laterality determination in wildtype specimens. Deviations from this norm come in different flavors. At the level of organ morphogenesis, laterality may be inverted (situs inversus) or non-concordant with respect to the main body axis (situs ambiguus or heterotaxia). At the level of Nodal cascade gene activation, expression may be inverted, bilaterally induced, or absent. In a given genetic situation, patterns may be randomized or predominantly lacking laterality (absence or bilateral activation). We propose that the distributions of patterns observed may be indicative of the underlying molecular defects, with randomizations being primarily caused by defects in the flow-generating ciliary set-up, and symmetrical patterns being the result of impaired flow sensing, on the left, the right, or both sides. This prediction, the reasoning of which is detailed in this review, pinpoints functions of genes whose role in laterality determination have remained obscure.
内脏的左右不对称性是脊椎动物及其他生物广泛存在的特征。它最终由神经胚期胚胎侧板中胚层中Nodal信号级联的左不对称激活所控制，这是由左右组织者处细胞外液的纤毛驱动向左流动所导致的。这种情况在野生型标本的左右不对称性确定中被广泛接受。与这种标准的偏差有不同形式。在器官形态发生水平上，左右不对称性可能会反转（内脏反位）或与主体轴不一致（内脏位置不明确或内脏异位）。在Nodal级联基因激活水平上，表达可能会反转、双侧诱导或缺失。在特定的遗传情况下，模式可能是随机的或主要缺乏左右不对称性（缺失或双侧激活）。我们提出，观察到的模式分布可能表明潜在的分子缺陷，随机化主要是由产生流动的纤毛装置缺陷引起的，而对称模式是左侧、右侧或两侧的流动感知受损的结果。这一预测的推理在本综述中有详细阐述，它指出了在左右不对称性确定中作用仍不明确的基因的功能。
