导读：人类究竟是如何产生左右差别的，最终这种差异又如何导致了心脏生长在左边，而肝脏生长在右边。最新一项研究发现在典型的两侧对称性中，肠道内胚层对决定器官发育区域的信息传递有重要的作用。研究结果发表在2012年3月6日出版的PLoS Biology杂志上。
从表面上来看，我们似乎是两边对称的。其实我们内部的器官位置是典型的不对称。举个例子，人的心脏生长左边，而肝脏则是在右边。人体内部器官左右不对称是如何建立引起了研究人员注意和兴趣，不仅是因为它们内在生物学意义，还因为它们的医学应用。
在哺乳动物实验模型小鼠身上，大量研究表明，打破两侧对称性的初始事件出现在位于胚胎发育中轴线的特定器官胚胎节点上。节点上的这种最初的不对称性是如何使所有事件串联起来，将一侧的信息传递到胚胎内某一个较远的位置？这个问题困扰了该研究领域长达10年之久。此前的实验表明，这种串联会激活胚胎左侧的遗传回路，并最终导致非对称器官的形成。如果这种串联没有传递出去，则无法建立左右的不对称性。
Kat Hadjantonakis和凯特林癌症中心的同事报道说，胚胎节点形成的非对称信号跨越胚胎表层的上皮细胞而传遍整个胚胎。内胚层的上皮细胞包含着能分化成呼吸道、消化道和诸如肺、肝和胰脏等相关器官的原发性细胞。
Hadjantonakis和其同事观察，缺少HMG转录因子Sox17的小鼠胚胎在形成肠道内胚层时表现了缺陷，随后不能建立左右的非对称性。他们进一步论证，细胞间跨越肠道内胚层上皮组织上的间隙连接的交流构成了进行左右信息传递的机制。
Role of the Gut Endoderm in Relaying Left-Right Patterning in Mice
Manuel Viotti, Lei Niu, Song-Hai Shi, Anna-Katerina Hadjantonakis
Establishment of left-right (LR) asymmetry occurs after gastrulation commences and utilizes a conserved cascade of events. In the mouse, LR symmetry is broken at a midline structure, the node, and involves signal relay to the lateral plate, where it results in asymmetric organ morphogenesis. How information transmits from the node to the distantly situated lateral plate remains unclear. Noting that embryos lacking Sox17 exhibit defects in both gut endoderm formation and LR patterning, we investigated a potential connection between these two processes. We observed an endoderm-specific absence of the critical gap junction component, Connexin43 (Cx43), in Sox17 mutants. Iontophoretic dye injection experiments revealed planar gap junction coupling across the gut endoderm in wild-type but not Sox17 mutant embryos. They also revealed uncoupling of left and right sides of the gut endoderm in an isolated domain of gap junction intercellular communication at the midline, which in principle could function as a barrier to communication between the left and right sides of the embryo. The role for gap junction communication in LR patterning was confirmed by pharmacological inhibition, which molecularly recapitulated the mutant phenotype. Collectively, our data demonstrate that Cx43-mediated communication across gap junctions within the gut endoderm serves as a mechanism for information relay between node and lateral plate in a process that is critical for the establishment of LR asymmetry in mice.
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