Morita Kiyokazu, Flemming Anthony J, Sugihara Yukiko, Mochii Makoto, Suzuki Yo, Yoshida Satoru, Wood William B, Kohara Yuji, Leroi Armand M, Ueno Naoto
Department of Developmental Biology, National Institute for Basic Biology, The Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
EMBO J. 2002 Mar 1;21(5):1063-73. doi: 10.1093/emboj/21.5.1063.
Using cDNA-based array analysis combined with double-stranded RNA interference (dsRNAi), we have identified yk298h6 as a target gene of Caenorhabditis elegans TGF-beta signaling. Worms overexpressing dbl-1, a TGF-beta ligand, are 16% longer than wild type. Array analysis shows yk298h6 to be one of several genes suppressed in such worms. Disruption of yk298h6 function by dsRNAi also resulted in long worms, suggesting that it is a negative regulator of body length. yk298h6 was then mapped to, and shown to be identical to, lon-1, a known gene that affects body length. lon-1 encodes a 312 amino acid protein with a motif sequence that is conserved from plants to humans. Expression studies confirm that LON-1 is repressed by DBL-1, suggesting that LON-1 is a novel downstream component of the C.elegans TGF-beta growth regulation pathway. Consistent with this, LON-1 is expressed mainly in the larval and adult hypodermis and has dose-dependent effects on body length associated with changes in hypodermal ploidy, but not hypodermal cell proliferation.
通过基于cDNA的阵列分析结合双链RNA干扰(dsRNAi),我们已将yk298h6鉴定为秀丽隐杆线虫TGF-β信号传导的一个靶基因。过表达TGF-β配体dbl-1的线虫比野生型长16%。阵列分析表明yk298h6是此类线虫中被抑制的几个基因之一。通过dsRNAi破坏yk298h6的功能也导致线虫体长增加,这表明它是体长的负调节因子。然后,yk298h6被定位到并被证明与lon-1相同,lon-1是一个已知的影响体长的基因。lon-1编码一种含有312个氨基酸的蛋白质,其基序序列从植物到人类都保守。表达研究证实LON-1受DBL-1抑制,这表明LON-1是秀丽隐杆线虫TGF-β生长调节途径的一个新的下游成分。与此一致的是,LON-1主要在幼虫和成虫的皮下组织表达,并且对与皮下多倍体变化相关的体长有剂量依赖性影响,但对皮下细胞增殖没有影响。
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