Inhibition of ribosome biogenesis in the epidermis is sufficient to trigger organism-wide growth quiescence independently of nutritional status in C. elegans.
Inhibition of ribosome biogenesis in the epidermis is sufficient to trigger organism-wide growth quiescence independently of nutritional status in C. elegans.
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DOI：
10.1371/journal.pbio.3002276
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发表时间：
2023-08
期刊：
影响因子：
9.8
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中科院分区：
文献类型：
--
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器官间通讯对多细胞生物的生长、发育和体内平衡至关重要。细胞非自主抑制线索，限制组织特异性生长的变化，没有得到很好的表征，由于细胞消融方法的限制。在本研究中，我们利用生长素诱导的降解系统在C。线虫通过消耗必需因子（RPOA-2、GRWD-1或TSR-2）在时间和空间上调节核糖体生物发生。我们的研究结果表明，胚胎范围内的核糖体生物合成抑制诱导一个可逆的早期幼虫生长停滞，区别于饥饿或dauer阶段的独特的基因表达签名。当核糖体生物合成在体积相似的组织中受到抑制时，包括体壁肌肉、表皮、咽、肠或生殖系，它会导致整个生物体在不同程度上成比例地发育不良。我们表明，特异性抑制表皮中的核糖体生物合成足以引发生物体范围内的生长静止。表皮特异性核糖体耗竭导致幼虫生长停滞在L3阶段，减少生物体范围内的蛋白质合成，并诱导细胞非自主基因表达改变。进一步的分子分析揭示了分泌蛋白的过度表达，表明了一种生物体范围内的调节机制。我们发现，在表皮核糖体生物合成介导的生长静止中，致密核心囊泡（DCV）通路的一个组成部分--β-31起着重要的作用。我们的组织特异性敲除实验表明，表皮特异性核糖体生物合成抑制诱导的生物体范围内的生长静止是通过减少表皮中的unc-31表达来抑制的，但在神经元或体壁肌肉中则不然。类似地，IDA-1，DCV的膜相关蛋白，过表达，并且其在表皮中的敲低抑制了响应于表皮核糖体生物发生抑制的生物体范围内的生长静止。最后，当表皮核糖体生物合成被抑制时，我们观察到IDA-1标记的DCV斑点的总体增加，并且这些斑点存在于表皮细胞中或附近。总之，这些研究结果表明，一种新的机制，营养独立的多细胞生长协调启动后，核糖体生物合成抑制表皮组织。本研究利用生长素诱导的C. elegans揭示了一种新的，营养独立的生长协调机制，表明表皮中核糖体生物合成的特异性抑制可以触发生物体范围内的生长静止，可能通过分泌蛋白和致密核心囊泡途径启动。
Interorgan communication is crucial for multicellular organismal growth, development, and homeostasis. Cell nonautonomous inhibitory cues, which limit tissue-specific growth alterations, are not well characterized due to cell ablation approach limitations. In this study, we employed the auxin-inducible degradation system in C. elegans to temporally and spatially modulate ribosome biogenesis, through depletion of essential factors (RPOA-2, GRWD-1, or TSR-2). Our findings reveal that embryo-wide inhibition of ribosome biogenesis induces a reversible early larval growth quiescence, distinguished by a unique gene expression signature that is different from starvation or dauer stages. When ribosome biogenesis is inhibited in volumetrically similar tissues, including body wall muscle, epidermis, pharynx, intestine, or germ line, it results in proportionally stunted growth across the organism to different degrees. We show that specifically inhibiting ribosome biogenesis in the epidermis is sufficient to trigger an organism-wide growth quiescence. Epidermis-specific ribosome depletion leads to larval growth quiescence at the L3 stage, reduces organism-wide protein synthesis, and induced cell nonautonomous gene expression alterations. Further molecular analysis reveals overexpression of secreted proteins, suggesting an organism-wide regulatory mechanism. We find that UNC-31, a dense-core vesicle (DCV) pathway component, plays a significant role in epidermal ribosome biogenesis-mediated growth quiescence. Our tissue-specific knockdown experiments reveal that the organism-wide growth quiescence induced by epidermal-specific ribosome biogenesis inhibition is suppressed by reducing unc-31 expression in the epidermis, but not in neurons or body wall muscles. Similarly, IDA-1, a membrane-associated protein of the DCV, is overexpressed, and its knockdown in epidermis suppresses the organism-wide growth quiescence in response to epidermal ribosome biogenesis inhibition. Finally, we observe an overall increase in DCV puncta labeled by IDA-1 when epidermal ribosome biogenesis is inhibited, and these puncta are present in or near epidermal cells. In conclusion, these findings suggest a novel mechanism of nutrition-independent multicellular growth coordination initiated from the epidermis tissue upon ribosome biogenesis inhibition. This study uses auxin-inducible degradation in C. elegans to reveal a novel, nutrition-independent mechanism of growth coordination, showing that specific inhibition of ribosome biogenesis in the epidermis can trigger an organism-wide growth quiescence, potentially initiated via secreted proteins and the dense-core vesicle pathway.
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影响因子：
11.8
作者：
Boulan, Laura;Andersen, Ditte;Leopold, Pierre
通讯作者：
Leopold, Pierre
影响因子：
--
作者：
Copenhaver, WM
通讯作者：
Copenhaver, WM
影响因子：
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作者：
Froehlich JJ;Rajewsky N;Ewald CY
通讯作者：
Ewald CY
影响因子：
11.8
作者：
Cenik, Elif Sarinay;Meng, Xuefeng;Fire, Andrew
通讯作者：
Fire, Andrew
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A