Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty
Synthetic mammalian pattern formation driven by differential diffusivity of Nodal and Lefty
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DOI：
10.1038/s41467-018-07847-x
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发表时间：
2018-12-21
影响因子：
16.6
通讯作者：
Ebisuya, Miki
中科院分区：
文献类型：
--
作者：
Sekine, Ryoji;Shibata, Tatsuo;Ebisuya, Miki
合成的哺乳动物反应扩散模式尚未创建，并且已提出 Nodal-Lefty 信号传导以满足模式形成的条件：Nodal 是短程激活剂，而 Lefty 是远程抑制剂。然而，这种模式形成的可能性从未被直接测试过，并且 Nodal 和 Lefty 差异扩散率的潜在机制仍不清楚。在这里，通过综合和理论方法的结合，我们表明哺乳动物细胞中重建的Nodal-Lefty网络自发地产生了一种模式。令人惊讶的是，细胞外节点被限制在细胞下方，导致与 Lefty 相比分布较窄。短程分布需要Nodal的finger 1结构域，将finger 1结构域移植到Lefty中缩短了Lefty的分布，成功地阻止了模式形成。这些结果表明，Nodal 和 Lefty 之间定位和结构域结构的差异，结合激活剂-抑制剂拓扑结构，足以用于反应扩散模式。
A synthetic mammalian reaction-diffusion pattern has yet to be created, and Nodal-Lefty signaling has been proposed to meet conditions for pattern formation: Nodal is a short-range activator whereas Lefty is a long-range inhibitor. However, this pattern forming possibility has never been directly tested, and the underlying mechanisms of differential diffusivity of Nodal and Lefty remain unclear. Here, through a combination of synthetic and theoretical approaches, we show that a reconstituted Nodal-Lefty network in mammalian cells spontaneously gives rise to a pattern. Surprisingly, extracellular Nodal is confined underneath the cells, resulting in a narrow distribution compared with Lefty. The short-range distribution requires the finger 1 domain of Nodal, and transplantation of the finger 1 domain into Lefty shortens the distribution of Lefty, successfully preventing pattern formation. These results indicate that the differences in localization and domain structures between Nodal and Lefty, combined with the activator-inhibitor topology, are sufficient for reaction-diffusion patterning.