Retinoids regulate a developmental checkpoint for tissue regeneration in Drosophila.
Retinoids regulate a developmental checkpoint for tissue regeneration in Drosophila.
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DOI：
10.1016/j.cub.2010.01.038
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发表时间：
2010-03-09
期刊：
影响因子：
--
通讯作者：
Hariharan IK
中科院分区：
文献类型：
--
作者：
Halme A;Cheng M;Hariharan IK
黑腹果蝇幼虫具有显著的再生生长能力：对其成像盘（成体结构的幼虫前体）的损伤，会引起存活组织的强烈增殖反应。然而，与其他生物一样，发育过程和分化会限制果蝇组织的再生能力。在果蝇和其他全变性昆虫中进行的实验表明，无论是对想象组织的损伤还是对受损的想象椎间盘的移植，都会延迟变形的发生，在这个过程中，想象椎间盘经历形态发生并分化成它们的成年结构。因此，在果蝇中似乎存在一种机制，可以感知组织损伤并延长幼虫期，以协调组织再生与生物体的整体发育程序。然而，这种途径如何起作用仍然未知。在这里，我们证明了发育检查点通过抑制编码PTTH基因的转录来延长影像椎间盘损伤后的幼虫生长，PTTH是一种促进类固醇激素蜕皮激素释放的神经肽。通过基因筛选，我们发现了一种以前未被怀疑的类视黄醇生物合成在调节PTTH表达和延迟组织损伤发育中的作用。类视黄醛信号在几种脊椎动物再生模型中起着重要的作用，但尚未明确。我们的研究结果表明，果蝇的类维甲酸生物合成对于维持再生生长的许可条件是重要的。
Drosophila melanogaster larvae have a remarkable capacity for regenerative growth: Damage to their imaginal discs, the larval precursors of adult structures, elicits a robust proliferative response from the surviving tissue. However, as in other organisms, developmental progression and differentiation can restrict regenerative capacity of Drosophila tissues. Experiments in Drosophila and other holometabolous insects have demonstrated that either damage to imaginal tissues or transplantation of a damaged imaginal disc delays the onset of metamorphosis, a time when the imaginal discs undergo morphogenesis and differentiation into their adult structures. Therefore, in Drosophila there appears to be a mechanism that senses tissue damage and extends the larval phase to coordinate tissue regeneration with the overall developmental program of the organism. However, how such a pathway functions remains unknown. Here we demonstrate that a developmental checkpoint extends larval growth after imaginal disc damage by inhibiting the transcription of the gene encoding PTTH, a neuropeptide that promotes the release of the steroid hormone ecdysone. Using a genetic screen, we identify a previously unsuspected role for retinoid biosynthesis in regulating PTTH expression and delaying development in response to tissue damage. Retinoid signaling plays an important, but poorly defined role in several vertebrate regeneration models. Our findings demonstrate that retinoid biosynthesis in Drosophila is important for the maintenance of a permissive condition for regenerative growth.
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