Molecular mechanisms of limb regeneration: insights from regenerating legs of the cricket Gryllus bimaculatus
Molecular mechanisms of limb regeneration: insights from regenerating legs of the cricket Gryllus bimaculatus
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DOI：
10.1387/ijdb.180048ho
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发表时间：
2018-01-01
影响因子：
0.7
通讯作者：
Ohuchi, Hideyo
中科院分区：
文献类型：
--
作者：
Bando, Tetsuya;Mito, Taro;Ohuchi, Hideyo
本文综述了近年来关于蟋蟀腿再生的研究进展，重点介绍了双斑蟋蟀腿再生的研究进展。近年来的研究揭示了腿部再生过程中胚基形成、位置信息建立和表观遗传调控的分子机制。特别是这些研究为解释蟑螂腿再生过程的经典概念模型如极坐标模型、插层模型、边界模型、陡度模型等提供了分子基础。当一条腿被截肢时，通过激活Janus-kinase (Jak)/ signal - transductionand activator -of- transcription （STAT）通路形成胚芽。随后，Hedgehog/Wingless/Decapentaplegic/表皮生长因子（epidermal -growth factor）通路在胚芽中指导远端分化，被称为分子边界模型。该通路的下游靶点是远端转录因子（Dll）和腊肠转录因子（dac），它们是近端远端模式形成的关键调节因子。Dll和dac分别通过调控跗骨模式基因来指定胚芽的远端和近端区域。再生过程中腿部模式基因的表达可能受组蛋白H3K27甲基化（通过增强子-zeste和泛在转录-四肽-重复基因- x染色体）的表观遗传控制。对于缺失结构在截肢位置和最远端位置之间嵌入的分子机制，提出了Dachsous/Fat （Ds/Ft）陡峭度模型，其中Ds/Ft通路维持位置信息并通过dac表达决定腿的大小。从理论上验证了该模型可以解释用蟋蟀腿得到的实验结果。全基因组序列信息的可用性、再生依赖的RNA干扰和基因组编辑技术将使蟋蟀成为揭示腿部再生基因功能的理想模型系统。
This review summarizes recent advances in leg regeneration research, focusing on the cricket Gryllus bimaculatus. Recent studies have revealed molecular mechanisms on blastema formation, establishment of positional information, and epigenetic regulation during leg regeneration. Especially, these studies have provided molecular bases in classical conceptual models such as the polar coordinate model, the intercalation model, the boundary model, the steepness model, etc., which were proposed to interpret regeneration processes of the cockroach legs. When a leg is amputated, a blastema is formed through the activation of the Janus-kinase (Jak)/Signal-Transduction-and-Activator-of-Transcription (STAT) pathway. Subsequently, the Hedgehog/Wingless/Decapentaplegic/Epidermal-growth-factor pathways instruct distalization in the blastema, designated as the molecular boundary model. Downstream targets of this pathway are transcription factors Distal-less (Dll) and dachshund (dac), functioning as key regulators of proximodistal pattern formation. Dll and dac specify the distal and proximal regions in the blastema, respectively, through the regulation of tarsal patterning genes. The expression of leg patterning genes during regeneration may be epigenetically controlled by histone H3K27 methylation via Enhancer-of-zeste and Ubiquitously-transcribed-tetratricopeptide-repeat-gene-X-chromosome. For the molecular mechanism of intercalation of the missing structures between the amputated position and the most distal one, Dachsous/Fat (Ds/Ft) steepness model has been proposed, in which the Ds/Ft pathway maintains positional information and determines leg size through dac expression. This model was theoretically verified to interpret the experimental results obtained with cricket legs. Availability of whole-genome sequence information, regeneration-dependent RNA interference, and genome editing technique will have the cricket be an ideal model system to reveal gene functions in leg regeneration.