分割时钟同步中的多种Notch配体
Multiple Notch ligands in the synchronization of the segmentation clock
AI总结：
本文针对斑马鱼分割时钟中不同Delta配体的作用，提出Notch受体激活的两种理论模型（Delta二聚体激活与Delta单体激活），并讨论如何通过实验区分二者，揭示多配体系统实现灵活信号响应的机制。
摘要：
Notch信号是一种普遍存在且功能多样的细胞间信号系统，驱动生物组织中的集体行为和模式形成。在胚胎发育过程中，Notch参与产生集体生化振荡，从而形成脊椎动物的体节，其功能失效会导致胚胎缺陷。Delta家族的Notch配体是这种集体节律的关键组成部分，但尚不清楚具有不同特性的不同Delta配体如何参与在细胞之间传递信息。受斑马鱼分割时钟的启发，在这项工作中我们提出一种描述生化振荡器之间相互作用的理论，其中Notch受体同时被振荡性和非振荡性Delta配体结合。基于先前的体外结合研究，我们首先考虑Notch通过Delta二聚体激活。该假设与Notch信号受扰动条件下的实验观察一致。然后我们检验另一种假设，即Delta单体直接结合并激活Notch，并证明这第二个模型也能描述实验观察结果。我们表明，这两种假设为非振荡性配体赋予了不同的角色，即作为结合伙伴或作为基线信号。最后，我们讨论了用于区分这两种情形的实验。总体而言，这项工作突出了信号系统如何利用配体的多样性来产生灵活多样的响应。
英文摘要：
Notch signaling is a ubiquitous and versatile intercellular signaling system that drives collective behaviors and pattern formation in biological tissues. During embryonic development, Notch is involved in generation of collective biochemical oscillations that form the vertebrate body segments, and its failure results in embryonic defects. Notch ligands of the Delta family are key components of this collective rhythm, but it is unclear how different Delta ligands with distinct properties contribute to relaying information among cells. Motivated by the zebrafish segmentation clock, in this work we propose a theory describing interactions between biochemical oscillators, where Notch receptor is bound by both oscillatory and nonoscillatory Delta ligands. Based on previous in vitro binding studies, we first consider Notch activation by Delta dimers. This hypothesis is consistent with experimental observations in conditions of perturbed Notch signaling. Then we test an alternative hypothesis where Delta monomers directly bind and activate Notch, and show that this second model can also describe the experimental observations. We show that these two hypotheses assign different roles for a non-oscillatory ligand, as a binding partner or as a baseline signal. Finally, we discuss experiments to distinguish between the two scenarios. Broadly, this work highlights how a multiplicity of ligands may be harnessed by a signaling system to generate versatile responses.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
