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通过工程化的GFP梯度进行体内模式和生长控制
2020-10-17 23:00

英国弗朗西斯·克里克研究所Jean-Paul Vincent研究组发现,通过工程化的绿色荧光蛋白(GFP)梯度可进行体内模式和生长控制。该研究于2020年10月16日发表于《科学》杂志。

为了揭示形成吗啡肽梯度的最低要求,他们在果蝇翅原基中设计了合成的吗啡肽。他们显示一种惰性蛋白,GFP,可以在存在与表面相关的抗GFP纳米抗体的情况下形成可检测的基于扩散的梯度,通过捕获配体并限制组织的渗漏来调节梯度。接下来,他们将抗GFP纳米抗体融合到天然形态发生剂Dpp的受体上,使其对细胞外GFP产生响应。

在这些工程受体的存在下,GFP可以替代Dpp以在体内组织模式形成和生长。糖基磷脂酰肌醇(GPI)锚定的非信号受体的伴随表达进一步改善了模式形成,达到接近野生型的质量。理论上的争论表明,GPI锚固对于这些受体扩大梯度长度范围并同时减少渗漏可能很重要。

据介绍,形态发生梯度在发育过程中提供位置信息。

附:英文原文

Title: Patterning and growth control in vivo by an engineered GFP gradient

Author: Kristina S. Stapornwongkul, Marc de Gennes, Luca Cocconi, Guillaume Salbreux, Jean-Paul Vincent

Issue&Volume: 2020/10/16

Abstract: Morphogen gradients provide positional information during development. To uncover the minimal requirements for morphogen gradient formation, we have engineered a synthetic morphogen in Drosophila wing primordia. We show that an inert protein, green fluorescent protein (GFP), can form a detectable diffusion-based gradient in the presence of surface-associated anti-GFP nanobodies, which modulate the gradient by trapping the ligand and limiting leakage from the tissue. We next fused anti-GFP nanobodies to the receptors of Dpp, a natural morphogen, to render them responsive to extracellular GFP. In the presence of these engineered receptors, GFP could replace Dpp to organize patterning and growth in vivo. Concomitant expression of glycosylphosphatidylinositol (GPI)–anchored nonsignaling receptors further improved patterning, to near–wild-type quality. Theoretical arguments suggest that GPI anchorage could be important for these receptors to expand the gradient length scale while at the same time reducing leakage.

DOI: 10.1126/science.abb8205

Source: https://science.sciencemag.org/content/370/6514/321

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037
官方网址:https://www.sciencemag.org/
投稿链接:https://cts.sciencemag.org/scc/#/login

本期文章:《科学》:Volume 370 Issue 6514

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