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骨形态发生蛋白/节点信号通路比例的时间动态驱动组织特异性原肠胚形成形态发生。

Temporal dynamics of BMP/Nodal ratio drive tissue-specific gastrulation morphogenesis.

作者信息

Emig Alyssa A, Hansen Megan, Grimm Sandra, Coarfa Cristian, Lord Nathan D, Williams Margot Kossmann

机构信息

Center for Precision Environmental Health and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.

Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.

出版信息

Development. 2025 May 1;152(9). doi: 10.1242/dev.202931.

Abstract

Anteroposterior elongation of the vertebrate body plan is driven by convergence and extension (C&E) gastrulation movements in both the mesoderm and neuroectoderm, but how or whether molecular regulation of C&E differs between tissues remains an open question. Using a zebrafish explant model of anteroposterior axis extension, we show that C&E of the neuroectoderm and mesoderm can be uncoupled ex vivo, and that morphogenesis of individual tissues results from distinct morphogen signaling dynamics. Using precise temporal manipulation of BMP and Nodal signaling, we identify a critical developmental window during which high or low BMP/Nodal ratios induce neuroectoderm- or mesoderm-driven C&E, respectively. Increased BMP activity similarly enhances C&E specifically in the ectoderm of intact zebrafish gastrulae, highlighting the in vivo relevance of our findings. Together, these results demonstrate that temporal dynamics of BMP and Nodal morphogen signaling activate distinct morphogenetic programs governing C&E gastrulation movements within individual tissues.

摘要

脊椎动物身体结构的前后伸长是由中胚层和神经外胚层的汇聚延伸(C&E)原肠胚形成运动驱动的,但C&E在不同组织间的分子调控方式或是否存在差异仍是一个悬而未决的问题。利用斑马鱼前后轴延伸的外植体模型,我们发现神经外胚层和中胚层的C&E在体外可以解偶联,并且单个组织的形态发生源于不同的形态发生素信号动态变化。通过对BMP和Nodal信号进行精确的时间操纵,我们确定了一个关键的发育窗口,在此期间,高或低的BMP/Nodal比值分别诱导神经外胚层或中胚层驱动的C&E。增加BMP活性同样会特异性增强完整斑马鱼原肠胚外胚层中的C&E,突出了我们研究结果在体内的相关性。总之,这些结果表明,BMP和Nodal形态发生素信号的时间动态激活了不同的形态发生程序,这些程序控制着单个组织内的C&E原肠胚形成运动。

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本文引用的文献

1
Optogenetic control of Nodal signaling patterns.
Development. 2025 May 1;152(9). doi: 10.1242/dev.204506.
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Development. 2024 Feb 15;151(4). doi: 10.1242/dev.202316. Epub 2024 Feb 19.
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Time-integrated BMP signaling determines fate in a stem cell model for early human development.
Nat Commun. 2024 Feb 17;15(1):1471. doi: 10.1038/s41467-024-45719-9.
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Cell Rep. 2023 Apr 25;42(4):112351. doi: 10.1016/j.celrep.2023.112351. Epub 2023 Apr 4.
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J Vis Exp. 2021 Jul 30(173). doi: 10.3791/62797.
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PLoS Biol. 2021 Jan 22;19(1):e3001059. doi: 10.1371/journal.pbio.3001059. eCollection 2021 Jan.
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Optogenetic investigation of BMP target gene expression diversity.
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