The BMP ligand Pinhead together with Admp supports the robustness of embryonic patterning
The BMP ligand Pinhead together with Admp supports the robustness of embryonic patterning
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BMP 配体 Pinhead 与 Admp 一起支持胚胎模式的稳健性
DOI：
10.1126/sciadv.aau6455
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发表时间：
2019
期刊：
影响因子：
13.6
通讯作者：
Wang Q.
中科院分区：
文献类型：
--
作者：
Yan Y.;Ning G.;Li L.;Liu J.;Yang S.;Cao Y.;Wang Q.
面对骨形态发生蛋白(BMP)信号的变化，脊椎动物胚胎背腹轴是稳定的。然而，这种稳健性背后的分子机制仍未确定。在这项研究中，我们发现斑马鱼Pinhead和AdMP一起，通过微调BMP信号，在确保轴向模式的稳健性方面发挥了重要的补偿作用。Pinhead编码在早期原肠胚腹外侧边缘表达的BMP样配体。针头和Admpis的转录处于相反的调控下，而头端的耗尽会导致Adp转录的代偿性增加，反之亦然，导致突变体中正常的轴形成。BMP/Smad途径直接抑制Pinhead和Admp2的表达。当BMP信号被抑制或过度激活时，针头/Admp的表达相应地改变，从而允许自我调节。因此，本研究揭示了BMP信号和针头/ADMP之间的负反馈环路，通过缓冲BMP信号的波动有效地稳定了胚胎模式。
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.pinheadencodes a BMP-like ligand expressed in the ventrolateral margin of the early gastrula. Transcription ofpinheadandadmpis under opposing regulation, wherepinheaddepletion results in a compensatory increase inadmptranscription and vice versa, leading to normal axis formation inpinheadoradmpmutants. Expression ofpinheadandadmpis directly repressed by the BMP/Smad pathway. When BMP signals were inhibited or excessively activated,pinhead/admpexpression changed accordingly, allowing for self-regulation. Thus, this study reveals a negative feedback loop between BMP signaling andpinhead/admpthat effectively stabilizes embryonic patterning by buffering against fluctuations in BMP signaling.