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Erk活性的周期性抑制驱动顺序性体节分割
2022-12-18 17:15

美国辛辛那提儿童医院医疗中心Erturul M. Özbudak等研究人员合作发现,Erk活性的周期性抑制驱动顺序性体节分割。这一研究成果于2022年12月14日在线发表在国际学术期刊《自然》上。

研究人员开发了斑马鱼的时钟和双磷酸化Erk(ppErk)梯度的精确报告器。结果表明,Her1-Her7振荡器通过周期性地降低ppErk来驱动分节确立,因此将其振荡投射到ppErk梯度上。ppErk梯度的脉冲式抑制可以完全替代时钟的作用,而运动性的时钟波对顺序分节是不需要的。时钟在ppErk的上游发挥作用,而ppErk又能使相邻的细胞在斑马鱼中离散地建立体节的边界。分子不同的时钟和形态发生梯度在依次分节的物种中被发现。这些研究结果表明,多功能的时钟可以在不同的物种中建立顺序分节,只要它们能抑制梯度。

据悉,连续的分节形成了不同后生动物胚胎的模块化身体计划。体节发生建立了脊椎动物体轴的分节模式。前中胚层的分子分节时钟设定了体节形成的速度。然而,细胞如何在一个特定的位置形成节段边界仍不清楚。

附:英文原文

Title: Periodic inhibition of Erk activity drives sequential somite segmentation

Author: Simsek, M. Fethullah, Chandel, Angad Singh, Saparov, Didar, Zinani, Oriana Q. H., Clason, Nicholas, zbudak, Erturul M.

Issue&Volume: 2022-12-14

Abstract: Sequential segmentation creates modular body plans of diverse metazoan embryos1,2,3,4. Somitogenesis establishes the segmental pattern of the vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm sets the pace of somite formation4. However, how cells are primed to form a segment boundary at a specific location remains unclear. Here we developed precise reporters for the clock and double-phosphorylated Erk (ppErk) gradient in zebrafish. We show that the Her1–Her7 oscillator drives segmental commitment by periodically lowering ppErk, therefore projecting its oscillation onto the ppErk gradient. Pulsatile inhibition of the ppErk gradient can fully substitute for the role of the clock, and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of ppErk, which in turn enables neighbouring cells to discretely establish somite boundaries in zebrafish5. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species3,4,6,7,8. Our findings imply that versatile clocks may establish sequential segmentation in diverse species provided that they inhibit gradients.

DOI: 10.1038/s41586-022-05527-x

Source: https://www.nature.com/articles/s41586-022-05527-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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