Periodic inhibition of Erk activity drives sequential somite segmentation.
Periodic inhibition of Erk activity drives sequential somite segmentation.
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DOI：
10.1038/s41586-022-05527-x
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发表时间：
2023-01
期刊：
影响因子：
64.8
通讯作者：
Ozbudak, Ertugrul M.
中科院分区：
文献类型：
--
作者：
Simsek, M. Fethullah;Chandel, Angad Singh;Saparov, Didar;Zinani, Oriana Q. H.;Clason, Nicholas;Ozbudak, Ertugrul M.
顺序分割创建不同的后生动物胚胎模块化的身体计划。体细胞发生建立了脊椎动物体轴的节段模式。体节前中胚层（PSM）中的分子分裂时钟决定了体节形成的速度。然而，细胞如何在特定位置形成片段边界仍然未知。在这里，我们开发了精确的报告的时钟和双磷酸化ERK（ppERK）的梯度在斑马鱼。我们发现Her 1/7振荡器通过周期性降低ppERK来驱动节段性承诺，从而将其振荡投射到ppERK梯度上。脉冲抑制的ppERK梯度可以完全取代时钟的作用和运动时钟波是连续分割的。该时钟在ppERK的上游发挥作用，这反过来又使邻近细胞能够在斑马鱼中离散地建立体节边界。分子发散的时钟和形态梯度被确定在顺序分割的物种。我们的研究结果意味着多功能时钟可以建立顺序分割在不同的物种，只要他们抑制梯度。
Sequential segmentation creates modular body plans of diverse metazoan embryos. Somitogenesis establishes segmental pattern of vertebrate body axis. A molecular segmentation clock in the presomitic mesoderm (PSM) sets the pace of somite formation. However, how cells are primed to form a segment boundary at a specific location remained unknown. Here we developed precise reporters for the clock and double phosphorylated ERK (ppERK) gradient in zebrafish. We discovered that the Her1/7 oscillator drives segmental commitment by periodically lowering ppERK, thus projecting its oscillation on the ppERK gradient. Pulsatile inhibition of the ppERK gradient can fully substitute the role of the clock and kinematic clock waves are dispensable for sequential segmentation. The clock functions upstream of the ppERK, which in turn enables neighboring cells to discretely establish somite boundaries in zebrafish. Molecularly divergent clocks and morphogen gradients were identified in sequentially segmenting species. Our findings imply versatile clocks may establish sequential segmentation in diverse species as long as they inhibit gradients.
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