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Fgf 驱动的 Tbx 蛋白活性直接诱导 和 启动斑马鱼肌发生。

Fgf-driven Tbx protein activities directly induce and to initiate zebrafish myogenesis.

机构信息

Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, SE1 1UL, UK.

Randall Centre for Cell and Molecular Biophysics, New Hunt's House, Guy's Campus, King's College London, SE1 1UL, UK

出版信息

Development. 2020 Apr 28;147(8):dev184689. doi: 10.1242/dev.184689.

Abstract

Skeletal muscle derives from dorsal mesoderm formed during vertebrate gastrulation. Fibroblast growth factor (Fgf) signalling cooperates with Tbx transcription factors to promote dorsal mesoderm formation, but their role in myogenesis has been unclear. Using zebrafish, we show that dorsally derived Fgf signals act through Tbx16 and Tbxta to induce slow and fast trunk muscle precursors at distinct dorsoventral positions. Tbx16 binds to and directly activates the and genes, which are required for commitment to myogenesis. Tbx16 activity depends on Fgf signalling from the organiser. In contrast, Tbxta is not required for expression, but binds a specific site upstream of that is not bound by Tbx16 and drives (dependent on Fgf signals) expression in adaxial slow precursors, thereby initiating trunk myogenesis. After gastrulation, when similar muscle cell populations in the post-anal tail are generated from tailbud, declining Fgf signalling is less effective at initiating adaxial myogenesis, which is instead initiated by Hedgehog signalling from the notochord. Our findings suggest a hypothesis for ancestral vertebrate trunk myogenic patterning and how it was co-opted during tail evolution to generate similar muscle by new mechanisms.This article has an associated 'The people behind the papers' interview.

摘要

骨骼肌来源于脊椎动物原肠胚形成过程中的背侧中胚层。成纤维细胞生长因子 (Fgf) 信号与 Tbx 转录因子协同作用,促进背侧中胚层的形成,但它们在肌肉发生中的作用尚不清楚。我们使用斑马鱼表明,源自背侧的 Fgf 信号通过 Tbx16 和 Tbxta 作用,在不同的背腹位置诱导慢肌和快肌前体。Tbx16 结合并直接激活 和 基因,这些基因对于向肌肉发生的分化是必需的。Tbx16 的活性依赖于组织者的 Fgf 信号。相比之下,Tbxta 对于 的表达不是必需的,但结合了 上游的一个特定位点,该位点不被 Tbx16 结合,并驱动(依赖于 Fgf 信号)在背侧慢肌前体中的表达,从而启动躯干肌肉发生。在原肠胚形成后,当来自尾芽的后肛尾部具有相似的肌肉细胞群体时,下降的 Fgf 信号在启动背侧肌肉发生方面的效果较差,而 Hedgehog 信号从脊索开始启动背侧肌肉发生。我们的发现提出了一个关于祖先脊椎动物躯干肌肉发生模式的假说,以及它如何在尾巴进化过程中被重新利用,通过新的机制产生相似的肌肉。本文有一个相关的“论文背后的人物”采访。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b45e/7197714/7858130e0e3c/develop-147-184689-g1.jpg

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