Adhyapok Priyom, Norman James, Bagnat Michel, Di Talia Stefano
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710 USA.
Center for Quantitative Living Systems, Duke University Medical Center, Durham, NC 27710 USA.
bioRxiv. 2025 Sep 2:2025.08.28.672946. doi: 10.1101/2025.08.28.672946.
The generation of a periodic body plan is a fundamental property of vertebrates. While biological oscillators provide a mechanism for timing the formation of repeated structures, few examples of signaling oscillators have been identified in development. Here, we show that the addition of repeating mineralizing segments in the zebrafish notochord is timed by tissue-wide, synchronous oscillations of Erk activity. The oscillations are mediated by delayed negative feedback from spry and dusp and expression of the Egf ligand. The uniform increase in egf expression controls the emergence of the oscillations, revealing the mechanism controlling the onset of notochord segmentation. Together, our work reveals an instance of synchronous clocks timing a patterning process and controlling the development of the vertebral column from the notochord.
生成周期性身体结构是脊椎动物的一项基本特性。虽然生物振荡器为重复结构的形成提供了一种计时机制,但在发育过程中,信号振荡器的实例却鲜有发现。在此,我们表明,斑马鱼脊索中重复矿化节段的添加是由全组织范围的、同步的Erk活性振荡来计时的。这些振荡由spry和dusp的延迟负反馈以及表皮生长因子(Egf)配体的表达介导。Egf表达的均匀增加控制了振荡的出现,揭示了控制脊索节段化起始的机制。我们的研究共同揭示了一个同步时钟计时模式形成过程并控制从脊索发育出脊柱的实例。