Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila
Shar-pei mediates cell proliferation arrest during imaginal disc growth in Drosophila
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DOI：
10.1242/dev.00168
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发表时间：
2002-12-01
期刊：
影响因子：
4.6
通讯作者：
Halder, G
中科院分区：
文献类型：
--
作者：
Kango-Singh, M;Nolo, R;Halder, G
在动物发育过程中，器官大小主要由细胞增殖的数量决定，必须严格调节细胞增殖的数量，以确保生成比例适当的器官。然而，当一个器官达到适当的大小时，指导细胞停止增殖的分子途径却知之甚少。我们已经确定了一个新的基因，shar-pei，这是必要的果蝇成虫盘发育过程中的细胞增殖的适当终止突变。在成虫盘中的shar-pei突变细胞的克隆产生含有更多正常大小细胞的增大的组织。我们表明，这种表型是细胞增殖增加和细胞凋亡减少的结果。因此，沙皮限制细胞增殖并促进细胞凋亡。相比之下，shar-pei不是成体组织的细胞分化和图案形成所必需的。Shar-pei也不需要在终末分化过程中退出细胞周期，这表明在器官生长过程中指导细胞增殖停滞的机制与在终末分化过程中指导细胞周期退出的机制不同。shar-pei编码一种含有WW-domain的蛋白质，在蠕虫、小鼠和人类中具有同源物，这表明器官生长控制机制在进化上是保守的。
During animal development, organ size is determined primarily by the amount of cell proliferation, which must be tightly regulated to ensure the generation of properly proportioned organs. However, little is known about the molecular pathways that direct cells to stop proliferating when an organ has attained its proper size. We have identified mutations in a novel gene, shar-pei, that is required for proper termination of cell proliferation during Drosophila imaginal disc development. Clones of shar-pei mutant cells in imaginal discs produce enlarged tissues containing more cells of normal size. We show that this phenotype is the result of both increased cell proliferation and reduced apoptosis. Hence, shar-pei restricts cell proliferation and promotes apoptosis. By contrast, shar-pei is not required for cell differentiation and pattern formation of adult tissue. Shar-pei is also not required for cell cycle exit during terminal differentiation, indicating that the mechanisms directing cell proliferation arrest during organ growth are distinct from those directing cell cycle exit during terminal differentiation. shar-pei encodes a WW-domain-containing protein that has homologs in worms, mice and humans, suggesting that mechanisms of organ growth control are evolutionarily conserved.