剖析胚胎缩放之谜:缩放假说及其在海胆胚胎中的证实

IF 2.1 4区 生物学 Q3 DEVELOPMENTAL BIOLOGY
Polina S Timoshina, Alexey M Nesterenko, Elena A Parshina, Eugeny E Orlov, Fedor M Eroshkin, Andrey G Zaraisky
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引用次数: 0

摘要

胚胎缩放是指胚胎根据大小调节其空间结构的能力,它仍然是发育生物学中一个引人入胜但研究不多的问题。这一现象最早由汉斯-德里希(Hans Driesch)在海胆胚胎中描述,现在已被认为是生物体如何利用非平衡自组织(基于反应-扩散(RD)系统)产生决定模式的形态发生器浓度梯度(随大小而扩展)的一个突出例子。虽然在某些情况下已经描述了这种梯度缩放的特定分子机制,但直到最近才开发出有针对性地识别这种机制的通用方法。为了寻找解决方案,我们假设特殊基因必须参与缩放机制,并将其命名为 "缩放器"。我们认为这些基因有两个共同的关键特征:它们的表达对胚胎大小很敏感,它们的蛋白产物决定了形态发生器浓度梯度的大小。作为原理证明,我们最近通过检测野生型和半大小爪爪蟹胃胚胎中不同表达的基因,确定了缩放器。此外,我们还描述了已发现的缩放器之一--编码金属蛋白酶 3(Mmp3)的基因--调节形态发生蛋白 Bmp 及其拮抗剂 Chordin 和 Noggin1/2 梯度缩放的机制。在本研究中,我们对 "缩放器假说"(Scalers Hypothesis)进行了重要的理论概括,证明了在产生形态发生浓度梯度的封闭 RD 系统中必须存在缩放器。此外,通过对所有已知类型的基于 RD 系统的胚胎缩放模型进行系统分析,我们证明了缩放器或明或暗地存在于所有已知类型的此类模型中。最后,为了检验 "缩放器假说 "的普遍性,我们应用我们的方法识别了根据海胆胚胎(Strongylocentrotus droebachiensis)的大小调整 Bmp/Chordin 梯度的缩放器。我们的研究结果表明,编码Span家族astacin金属蛋白酶的基因簇中至少有两个成员(即bp10和Span)表现出了缩放器的特性。也就是说,它们在半大胚胎中的表达水平显著增加,其蛋白产物能特异性地降解 Chordin。此外,我们发现 bp10 和 span 的功能缺失会导致 Bmp 信号核效应子 pSmad1/5 的背侧结构域变窄。这些发现不仅验证了 "Scalers假说",而且揭示了一种新的机制,即Span蛋白酶可微调海胆中Chordin和Bmp形态发生因子的浓度梯度。因此,"缩放假说 "和在其基础上开发的定向搜寻此类基因的方法为未来研究各种生物系统中的缩放机制开辟了前景广阔的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dissecting the mystery of embryonic scaling: The Scalers Hypothesis and its confirmation in sea urchin embryos.

Embryonic scaling, the ability of embryos to regulate their spatial structure in proportion to size, remains a fascinating yet poorly studied problem in developmental biology. First described in sea urchin embryos by Hans Driesch, this phenomenon is now recognized as a striking example of how living organisms use non-equilibrium self-organization, based on reaction-diffusion (RD) systems, to generate pattern-determining morphogen concentration gradients that scale with size. Although specific molecular mechanisms for scaling such gradients have been described in some cases, a general approach for the targeted identification of such mechanisms had not been developed until recently. In search of a solution, we hypothesized the obligatory participation in scaling mechanisms of special genes, which we named "scalers." We supposed that these genes share two critical features: their expression is sensitive to embryo size, and their protein products determine the scale of morphogen concentration gradients. As proof of principle, we recently identified scalers by detecting differentially expressed genes in wild-type and half-size Xenopus laevis gastrula embryos. Furthermore, we described a mechanism by which one of the identified scalers, the gene encoding Metalloproteinase 3 (Mmp3), regulates the scaling of gradients of the morphogenic protein Bmp and its antagonists, Chordin and Noggin1/2. In the present work, we have made an important theoretical generalization of the Scalers Hypothesis by proving a statement regarding the obligatory presence of scalers in closed RD systems generating morphogen concentration gradients. Furthermore, through a systematic analysis of all known types of embryonic scaling models based on RD systems, we demonstrate that scalers are present in all known types of such models, either explicitly or implicitly. Finally, to test the universality of the Scalers Hypothesis, we applied our method to identify scalers that adjust Bmp/Chordin gradients to the size of the sea urchin embryo, Strongylocentrotus droebachiensis. Our results show that at least two members of the gene cluster encoding astacin metalloproteinases of the Span family, namely bp10 and Span, exhibit properties characteristic of scalers. Namely, their expression levels increase significantly in half-size embryos, and their protein products specifically degrade Chordin. Additionally, we found that the loss of function of bp10 and span leads to a narrowing of the dorsal domain of the Bmp signaling nuclear effector, pSmad1/5. These findings not only validate the Scalers Hypothesis but also uncover a novel mechanism by which Span proteinases fine-tune Chordin and Bmp morphogen concentration gradients in sea urchins. Thus, the Scalers Hypothesis and the approach to targeted search for such genes developed on its basis open up promising avenues for future research into scaling mechanisms in various biological systems.

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来源期刊
Cells & Development
Cells & Development DEVELOPMENTAL BIOLOGY-
CiteScore
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