Genetic Screen in Drosophila melanogaster Uncovers a Novel Set of Genes Required for Embryonic Epithelial Repair
Genetic Screen in Drosophila melanogaster Uncovers a Novel Set of Genes Required for Embryonic Epithelial Repair
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DOI：
10.1534/genetics.109.110288
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发表时间：
2010-01-01
期刊：
影响因子：
3.3
通讯作者：
Jacinto, Antonio
中科院分区：
文献类型：
--
作者：
Campos, Isabel;Geiger, Jennifer A.;Jacinto, Antonio
伤口愈合反应是维持上皮完整性和保护所有生物体免受周围环境影响的重要机制。在伤口闭合的“荷包-细绳”机制中，受损的上皮层通过细胞间收缩性肌动球蛋白索将其孔收紧闭合。这一过程在物种间是保守的，并被胚胎和成体组织所利用，但在细胞水平上仍然知之甚少。为了确定参与荷包缝合伤口的新参与者，我们开发了一种适合筛选大量果蝇胚胎的创伤策略。使用这种方法，我们观察伤口愈合的缺陷，在Jun-related抗原（编码DJUN）和结痂（编码果蝇α PS3整联蛋白）突变体，并进行了正向遗传学筛选的基础上，插入突变的转座子，导致30个致命的插入突变体的鉴定与胚胎上皮修复缺陷。鉴定的突变体之一是喀斯特基因座中的插入，其编码果蝇β（重）-血影蛋白。我们显示β（重）-血影蛋白（β（H））定位于伤口边缘，在那里它可能发挥使伤口正常闭合的基本功能。
The wound healing response is an essential mechanism to maintain the integrity of epithelia and protect all organisms from the surrounding milieu. In the "purse-string'' mechanism of wound closure, an injured epithelial sheet cinches its hole closed via an intercellular contractile actomyosin cable. This process is conserved across species and utilized by both embryonic as well as adult tissues, but remains poorly understood at the cellular level. In an effort to identify new players involved in purse-string wound closure we developed a wounding strategy suitable for screening large numbers of Drosophila embryos. Using this methodology, we observe wound healing defects in Jun-related antigen (encoding DJUN) and scab (encoding Drosophila alpha PS3 integrin) mutants and performed a forward genetics screen on the basis of insertional mutagenesis by transposons that led to the identification of 30 lethal insertional mutants with defects in embryonic epithelia repair. One of the mutants identified is an insertion in the karst locus, which encodes Drosophila beta(Heavy)-spectrin. We show beta(Heavy)-spectrin (beta(H)) localization to the wound edges where it presumably exerts an essential function to bring the wound to normal closure.