Eroshkin Fedor M, Nesterenko Alexey M, Borodulin Alexander V, Martynova Natalia Yu, Ermakova Galina V, Gyoeva Fatima K, Orlov Eugeny E, Belogurov Alexey A, Lukyanov Konstantin A, Bayramov Andrey V, Zaraisky Andrey G
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie gory, 1/40, 119991 Moscow, Russia.
Sci Rep. 2016 Mar 14;6:23049. doi: 10.1038/srep23049.
Noggin4 is a Noggin family secreted protein whose molecular and physiological functions remain unknown. In this study, we demonstrate that in contrast to other Noggins, Xenopus laevis Noggin4 cannot antagonise BMP signalling; instead, it specifically binds to Wnt8 and inhibits the Wnt/β -catenin pathway. Live imaging demonstrated that Noggin4 diffusivity in embryonic tissues significantly exceeded that of other Noggins. Using the Fluorescence Recovery After Photobleaching (FRAP) assay and mathematical modelling, we directly estimated the affinity of Noggin4 for Wnt8 in living embryos and determined that Noggin4 fine-tune the Wnt8 posterior-to-anterior gradient. Our results suggest a role for Noggin4 as a unique, freely diffusing, long-range inhibitor of canonical Wnt signalling, thus explaining its ability to promote head development.
Noggin4是一种Noggin家族分泌蛋白，其分子和生理功能尚不清楚。在本研究中，我们证明，与其他Noggin不同，非洲爪蟾Noggin4不能拮抗骨形态发生蛋白（BMP）信号；相反，它特异性结合Wnt8并抑制Wnt/β-连环蛋白信号通路。实时成像显示，Noggin4在胚胎组织中的扩散率显著超过其他Noggin。使用光漂白后荧光恢复（FRAP）分析和数学建模，我们直接估计了Noggin4与活胚胎中Wnt8的亲和力，并确定Noggin4微调了Wnt8从后到前的梯度。我们的结果表明，Noggin4作为经典Wnt信号的一种独特的、自由扩散的、长距离抑制剂发挥作用，从而解释了其促进头部发育的能力。
