Scaling of Dorsal-Ventral Patterning by Embryo Size-Dependent Degradation of Spemann's Organizer Signals
Scaling of Dorsal-Ventral Patterning by Embryo Size-Dependent Degradation of Spemann's Organizer Signals
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DOI：
10.1016/j.cell.2013.05.004
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发表时间：
2013-06-06
期刊：
影响因子：
64.5
通讯作者：
Sasai, Yoshiki
中科院分区：
文献类型：
--
作者：
Inomata, Hidehiko;Shibata, Tatsuo;Sasai, Yoshiki
Spemann的组织者通过分泌可扩散的蛋白质在两栖动物胚胎的背腹(DV)模式中发挥关键作用，例如Chordin，一种对骨形态发生蛋白(BMPs)腹化的拮抗剂。DV模式是如此强大，以至于手术切除腹侧一半的两栖动物胚胎可以发育成更小但有比例模式的幼虫。在这里，我们表明，这种健壮的模式依赖于促进的骨胶原降解，并需要表达的丝氨酸蛋白水解酶抑制剂在相反的方面。稳定并沿DV轴广泛扩散的sizzed，稳定了Chordin并扩大了其在腹侧的分布。这种扩大的Chordin分布反过来限制了BMP依赖的刺激性生产，形成了塑造Chordin活性的轴向反馈回路。使用二分分析，我们证明了胚大小耦合的嘶嘶声积累动态地控制了骨胶原的降解。我们提出了一个缩放模型，使DV模式能够按比例调整到胚胎轴的大小。
Spemann's organizer plays a key role in dorsal-ventral (DV) patterning in the amphibian embryo by secreting diffusible proteins such as Chordin, an antagonist to ventralizing bone morphogenetic proteins (BMPs). The DV patterning is so robust that an amphibian embryo with its ventral half surgically removed can develop into a smaller but proportionally patterned larva. Here, we show that this robust patterning depends on facilitated Chordin degradation and requires the expression of the Chordin-proteinase inhibitor Sizzled on the opposite side. Sizzled, which is stable and diffuses widely along the DV axis, stabilizes Chordin and expands its distribution in the ventral direction. This expanded Chordin distribution, in turn, limits BMP-dependent Sizzled production, forming an axis-wide feedback loop for shaping Chordin's activity. Using bisection assays, we demonstrate that Chordin degradation is dynamically controlled by embryo-size-coupled Sizzled accumulation. We propose a scaling model that enables the DV pattern to adjust proportionally to embryonic axis size.