State Key Laboratory of Membrane Biology, Institute of Zoology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100101, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China.
Sci Adv. 2019 Dec 18;5(12):eaau6455. doi: 10.1126/sciadv.aau6455. eCollection 2019 Dec.
Vertebrate embryonic dorsoventral axis is robustly stable in the face of variations in bone morphogenetic protein (BMP) signaling. However, the molecular mechanism behind this robustness remains uncharacterized. In this study, we show that zebrafish Pinhead, together with Admp, plays an important compensatory role in ensuring the robustness of axial patterning through fine-tuning of BMP signaling. encodes a BMP-like ligand expressed in the ventrolateral margin of the early gastrula. Transcription of and is under opposing regulation, where depletion results in a compensatory increase in transcription and vice versa, leading to normal axis formation in or mutants. Expression of and is directly repressed by the BMP/Smad pathway. When BMP signals were inhibited or excessively activated, / expression changed accordingly, allowing for self-regulation. Thus, this study reveals a negative feedback loop between BMP signaling and that effectively stabilizes embryonic patterning by buffering against fluctuations in BMP signaling.
脊椎动物胚胎背腹轴在面对骨形态发生蛋白（BMP）信号变化时具有强大的稳定性。然而，这种稳健性背后的分子机制仍未被阐明。在这项研究中，我们表明斑马鱼 Pinhead 与 Admp 一起，通过精细调节 BMP 信号，在确保轴向模式形成的稳健性方面发挥了重要的补偿作用。 编码一种在早期原肠胚的腹侧缘表达的 BMP 样配体。 的转录受到相反的调控， 缺失导致 的转录代偿性增加，反之亦然，导致 或 突变体中正常的轴形成。 和 的表达受到 BMP/Smad 途径的直接抑制。当 BMP 信号被抑制或过度激活时，/的表达相应改变，从而实现自我调节。因此，这项研究揭示了 BMP 信号与 之间的负反馈回路，通过缓冲 BMP 信号的波动，有效地稳定了胚胎模式形成。
