Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation.
Notch-dependent and -independent transcription are modulated by tissue movements at gastrulation.
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DOI：
10.7554/elife.73656
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发表时间：
2022-05-18
期刊：
影响因子：
7.7
通讯作者：
Bray, Sarah
中科院分区：
文献类型：
--
作者：
Falo-Sanjuan, Julia;Bray, Sarah
细胞感知并整合来自不同来源的外部信息，包括机械线索。因此，在发育过程中组织的成形可能需要来自形态发生的机械力和细胞-细胞信号传导之间的协调，以赋予基因表达的适当变化。通过真实的实时成像Notch诱导的转录，我们发现果蝇原肠胚形成期间的形态发生运动引起Notch响应增强子活性水平的增加。破坏原肠胚形成时间的突变导致与中胚层内陷开始相关的转录上调的伴随延迟。由于当转录由细胞内结构域NICD引起时检测到类似的原肠胚诱导效应，因此不能将其归因于施加在Notch受体活化上的力。Notch非依赖性vnd增强子也在同一条细胞中表现出适度的原肠胚诱导活性增加。总之，这些观察结果表明，原肠胚相关的力量作用于细胞核，以调节转录水平。当连接核骨架和细胞骨架（LINC）的复合物被破坏时，这种调节被解偶联，表明可能存在管道。我们建议，组织水平的力学，所产生的原肠胚形成，和增强子活性之间的耦合代表了一个一般的机制，以确保正确的组织规格在发展过程中，Notch依赖性增强子是高度敏感的这种调节。
Cells sense and integrate external information from diverse sources that include mechanical cues. Shaping of tissues during development may thus require coordination between mechanical forces from morphogenesis and cell-cell signalling to confer appropriate changes in gene expression. By live-imaging Notch-induced transcription in real time, we have discovered that morphogenetic movements during Drosophila gastrulation bring about an increase in activity-levels of a Notch-responsive enhancer. Mutations that disrupt the timing of gastrulation resulted in concomitant delays in transcription up-regulation that correlated with the start of mesoderm invagination. As a similar gastrulation-induced effect was detected when transcription was elicited by the intracellular domain NICD, it cannot be attributed to forces exerted on Notch receptor activation. A Notch-independent vnd enhancer also exhibited a modest gastrulation-induced activity increase in the same stripe of cells. Together, these observations argue that gastrulation-associated forces act on the nucleus to modulate transcription levels. This regulation was uncoupled when the complex linking the nucleoskeleton and cytoskeleton (LINC) was disrupted, indicating a likely conduit. We propose that the coupling between tissue-level mechanics, arising from gastrulation, and enhancer activity represents a general mechanism for ensuring correct tissue specification during development and that Notch-dependent enhancers are highly sensitive to this regulation.