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上皮细胞更新确保了果蝇核糖体蛋白突变体中组织生长的稳健协调。

Epithelial cell-turnover ensures robust coordination of tissue growth in Drosophila ribosomal protein mutants.

机构信息

Laboratory of Genetics, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.

Group of Genetics, Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Japan.

出版信息

PLoS Genet. 2021 Jan 28;17(1):e1009300. doi: 10.1371/journal.pgen.1009300. eCollection 2021 Jan.

Abstract

Highly reproducible tissue development is achieved by robust, time-dependent coordination of cell proliferation and cell death. To study the mechanisms underlying robust tissue growth, we analyzed the developmental process of wing imaginal discs in Drosophila Minute mutants, a series of heterozygous mutants for a ribosomal protein gene. Minute animals show significant developmental delay during the larval period but develop into essentially normal flies, suggesting there exists a mechanism ensuring robust tissue growth during abnormally prolonged developmental time. Surprisingly, we found that both cell death and compensatory cell proliferation were dramatically increased in developing wing pouches of Minute animals. Blocking the cell-turnover by inhibiting cell death resulted in morphological defects, indicating the essential role of cell-turnover in Minute wing morphogenesis. Our analyses showed that Minute wing discs elevate Wg expression and JNK-mediated Dilp8 expression that causes developmental delay, both of which are necessary for the induction of cell-turnover. Furthermore, forced increase in Wg expression together with developmental delay caused by ecdysone depletion induced cell-turnover in the wing pouches of non-Minute animals. Our findings suggest a novel paradigm for robust coordination of tissue growth by cell-turnover, which is induced when developmental time axis is distorted.

摘要

高度可重现的组织发育是通过细胞增殖和细胞死亡的稳健、时间依赖性协调来实现的。为了研究稳健组织生长的机制,我们分析了果蝇 Minute 突变体的翅膀 imaginal 盘的发育过程,该突变体是一系列核糖体蛋白基因的杂合突变体。Minute 动物在幼虫期表现出明显的发育延迟,但发育成基本正常的苍蝇,这表明存在一种机制可以确保在异常延长的发育时间内稳健的组织生长。令人惊讶的是,我们发现 Minut 动物发育中的翅膀囊泡中的细胞死亡和代偿性细胞增殖都显著增加。通过抑制细胞死亡来阻止细胞更替会导致形态缺陷,表明细胞更替在 Minute 翅膀形态发生中起着重要作用。我们的分析表明,Minute 翅膀盘会提高 Wg 表达和 JNK 介导的 Dilp8 表达,从而导致发育延迟,这两者对于诱导细胞更替都是必需的。此外,强制增加 Wg 表达并结合蜕皮激素耗竭引起的发育延迟会导致非 Minute 动物的翅膀囊中发生细胞更替。我们的发现表明,通过细胞更替稳健协调组织生长的新范例,当发育时间轴发生扭曲时,就会诱导细胞更替。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cfd7/7842893/a27b3fb8a4b5/pgen.1009300.g001.jpg

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