Discussing limb development and regeneration in Barcelona: The future is at hand.
Discussing limb development and regeneration in Barcelona: The future is at hand.
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在巴塞罗那讨论肢体发育和再生：未来就在眼前。
DOI：
10.1002/dvdy.121
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Whited,JessicaL
中科院分区：
文献类型：
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作者：
Rosello-Diez,Alberto;Whited,JessicaL
7月2日至5日，巴塞罗那市举办了EMBO肢体发育和再生研讨会（第15届国际会议）。来自世界各地的科学家们沐浴在海边西班牙城市的温暖之中，展示并讨论了这一经典领域的新发展，这一领域迅速而巨大地受益于最先进工具的使用。在此，我们对肢体发育和再生的基因调控、模式、形态发生、生长和进化等方面的最新进展进行了综述。基因调控领域以新方法的使用为主导。主讲人Len Pennacchio （Lawrence Berkeley Laboratory, Berkeley， CA）的实验室开发了一种基于H3K27ac或P300峰强度的增强子排序方法，这与元素的活性密切相关。此外，他们通过CRISPR/Cas9使用靶向插入改进了转基因检测，最大限度地减少了非特异性和沉默效应。效率的提高现在允许对整个监管区域进行高分辨率的询问。继续介绍新方法，James Sharpe （EMBL Barcelona, Spain）对其团队开发的新工具LIMB-NET进行了现场演示。这个基于浏览器的应用程序允许用户上传、编辑和测试感兴趣的基因调控网络的不同模型，在小鼠肢体生长的2D模型上模拟结果，并交互式地探索随着时间和空间的预测基因表达模式。除了新工具，会议的一个共同主题是监管的稳健性。Aimee Zuniga（瑞士巴塞尔大学）描述了一个富含Grem1增强子的小TAD，去除它会产生功能丧失表型。令人惊讶的是，去除这些增强子中的一些会导致对表达或骨骼表型的微弱影响或没有影响，显示出显着的稳健性，这可能是由于某些区域缺失时染色质相互作用的可塑性。Denis Duboule（瑞士日内瓦大学/EPFL）冒险展示了生殖器中5'Hox基因的调控。令人惊讶的是，当他们研究一个负责70% 5'Hox基因表达的区域时，他们发现四个假定的增强子序列中没有一个是单独调节所必需的。组合缺失是否以及如何影响基因表达还有待观察。关于一些转录因子如何起作用也有新的建议。Steve Vokes（德克萨斯大学奥斯汀分校）提供的证据表明，GLI蛋白通过募集组蛋白去乙酰化酶介导抑制，使增强子活性失活，而不影响组蛋白甲基化。Marie Kmita（加拿大蒙特利尔临床研究所）描述了HoxA13和HoxD13在促进染色质可及性方面的新作用，使其他转录因子能够结合它们的基序。这可能有助于建立机制
From July 2 to 5, the city of Barcelona hosted the EMBO Workshop on Limb Development and Regeneration (the 15th international meeting on this topic). Wrapped by the literal warmth of the Spanish city by the sea, scientists from all over the world presented and discussed the new developments of a classic field that has rapidly and enormously benefited from the use of state-of-the-art tools. Here, we present a summary of the latest advances on gene regulation, patterning, morphogenesis, growth, and evolution of limb development and regeneration. The Gene Regulation arena was dominated by the use of new approaches. The lab of keynote speaker Len Pennacchio (Lawrence Berkeley Laboratory, Berkeley, CA) has developed an enhancer ranking method based on the intensity of H3K27ac or P300 peaks, which correlates well with the activity of the element. Moreover, they have improved transgenic assays by using targeted insertion via CRISPR/Cas9, minimizing nonspecific and silencing effects. The increased efficiency now allows for highresolution interrogation of whole regulatory regions. Continuing with new approaches, James Sharpe (EMBL Barcelona, Spain) gave a live demo of the new tool his team has built, LIMB-NET. This browser-based application allows the user to upload, edit, and test different models of the gene regulatory networks of interest, simulate the outcome on a 2D model of mouse limb outgrowth, and interactively explore the predicted gene expression patterns over time and space. Besides new tools, a common theme in the session was the robustness of regulation. Aimee Zuniga (University of Basel, Switzerland) described a small TAD rich in enhancers for Grem1, the removal of which yields a loss-of-function phenotype. Surprisingly, removal of several of this enhancers lead to weak or no effect on expression or in skeletal phenotype, revealing remarkable robustness, probably due to plasticity of chromatin interactions upon deletion of some of these regions. Denis Duboule (University of Geneva/EPFL, Switzerland) went out on a limb to show regulation of 5'Hox genes in genitalia. Surprisingly, when they studied one region responsible for 70% of 5'Hox gene expression, they discovered that none of the four presumptive enhancer sequences was individually necessary for that regulation. It remains to be seen if and how combinatorial deletion impacts gene expression. There were also new proposals on how some transcription factors work. Steve Vokes (University of Texas at Austin, TX) showed evidence suggesting GLI proteins mediate repression via recruitment of histone deacetylases that deactivate enhancer activity without affecting histone methylation. Marie Kmita (Clinical Research Institute of Montreal, Canada) described new roles for HoxA13 and HoxD13 in facilitating chromatin accessibility, enabling other transcription factors to bind their motifs. This could contribute to mechanisms