The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network.
The Pax6 master control gene initiates spontaneous retinal development via a self-organising Turing network.
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DOI：
10.1242/dev.185827
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发表时间：
2020-12-23
期刊：
影响因子：
--
通讯作者：
Münsterberg AE
中科院分区：
文献类型：
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作者：
Grocott T;Lozano-Velasco E;Mok GF;Münsterberg AE
了解复杂的器官系统是如何从简单的胚胎组织组装起来的是一个重大挑战。在动物王国中，各种各样的视觉器官都是由一种名为Pax6的“主控基因”启动的，这种基因对眼睛的发育既必要又足够。然而，Pax6究竟是如何实现这种高度同源的功能的，人们还知之甚少。使用鸡作为模式生物，我们表明，脊椎动物Pax6相互作用的一对形态发生编码基因，Tgfb2和Fst，形成一个假定的图灵网络，我们已经计算建模。计算机模拟表明，这种基因网络足以自发地极化发育中的视网膜，建立眼睛的第一个组织轴，并预示着它的进一步发展。我们的研究结果揭示了视网膜的自我组织是如何独立于有助于在体内组装眼睛的高度有序的组织相互作用而启动的。这些结果有助于解释干细胞聚集体如何在体外自发地自组织成功能性眼杯。我们预计这些发现将有助于支持视网膜类器官技术，该技术作为疾病建模，药物开发和再生疗法的平台具有很大的希望。 Pax6可以在体内诱导异位眼发育，而视网膜类器官可以在体外自组织。我们发现一个Pax6图灵网络可以解释这两种现象。
Understanding how complex organ systems are assembled from simple embryonic tissues is a major challenge. Across the animal kingdom a great diversity of visual organs are initiated by a ‘master control gene’ called Pax6, which is both necessary and sufficient for eye development. Yet precisely how Pax6 achieves this deeply homologous function is poorly understood. Using the chick as a model organism, we show that vertebrate Pax6 interacts with a pair of morphogen-coding genes, Tgfb2 and Fst, to form a putative Turing network, which we have computationally modelled. Computer simulations suggest that this gene network is sufficient to spontaneously polarise the developing retina, establishing the first organisational axis of the eye and prefiguring its further development. Our findings reveal how retinal self-organisation may be initiated independently of the highly ordered tissue interactions that help to assemble the eye in vivo. These results help to explain how stem cell aggregates spontaneously self-organise into functional eye-cups in vitro. We anticipate these findings will help to underpin retinal organoid technology, which holds much promise as a platform for disease modelling, drug development and regenerative therapies. Pax6 can induce ectopic eye development in vivo, while retinal organoids can self-organise in vitro. We identify a Pax6 Turing network that could explain both phenomena.