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lmx1b基因在非洲爪蟾的球状体发育中起关键作用。

The lmx1b gene is pivotal in glomus development in Xenopus laevis.

作者信息

Haldin Caroline E, Massé Karine L, Bhamra Surinder, Simrick Subreena, Kyuno Jun-ichi, Jones Elizabeth A

机构信息

Department of Biological Sciences, Warwick University, Coventry, CV4 7AL, UK.

出版信息

Dev Biol. 2008 Oct 1;322(1):74-85. doi: 10.1016/j.ydbio.2008.07.012. Epub 2008 Jul 21.

Abstract

We have previously shown that lmx1b, a LIM homeodomain protein, is expressed in the pronephric glomus. We now show temporal and spatial expression patterns of lmx1b and its potential binding partners in both dissected pronephric anlagen and in individual dissected components of stage 42 pronephroi. Morpholino oligonucleotide knock-down of lmx1b establishes a role for lmx1b in the development of the pronephric components. Depletion of lmx1b results in the formation of a glomus with reduced size. Pronephric tubules were also shown to be reduced in structure and/or coiling whereas more distal tubule structure was unaffected. Over-expression of lmx1b mRNA resulted in no significant phenotype. Given that lmx1b protein is known to function as a heterodimer, we have over-expressed lmx1b mRNA alone or in combination with potential interacting molecules and analysed the effects on kidney structures. Phenotypes observed by over-expression of lim1 and ldb1 are partially rescued by co-injection with lmx1b mRNA. Animal cap experiments confirm that co-injection of lmx1b with potential binding partners can up-regulate pronephric molecular markers suggesting that lmx1b lies upstream of wt1 in the gene network controlling glomus differentiation. This places lmx1b in a genetic hierarchy involved in pronephros development and suggests that it is the balance in levels of binding partners together with restricted expression domains of lmx1b and lim1 which influences differentiation into glomus or tubule derivatives in vivo.

摘要

我们之前已经表明,一种LIM同源结构域蛋白lmx1b在前肾小球中表达。我们现在展示了lmx1b及其潜在结合伙伴在解剖的前肾原基以及42期前肾的各个解剖成分中的时空表达模式。通过吗啉代寡核苷酸敲低lmx1b确定了lmx1b在前肾成分发育中的作用。lmx1b的缺失导致形成尺寸减小的小球。还显示前肾小管在结构和/或盘绕方面减少,而更远端的肾小管结构未受影响。lmx1b mRNA的过表达未产生明显的表型。鉴于已知lmx1b蛋白作为异二聚体发挥作用,我们单独或与潜在的相互作用分子一起过表达lmx1b mRNA,并分析对肾脏结构的影响。通过与lmx1b mRNA共注射,观察到的lim1和ldb1过表达的表型部分得到挽救。动物帽实验证实,将lmx1b与潜在结合伙伴共注射可以上调前肾分子标记,这表明在控制小球分化的基因网络中,lmx1b位于wt1的上游。这将lmx1b置于参与前肾发育的遗传层次结构中,并表明正是结合伙伴水平的平衡以及lmx1b和lim1的受限表达域影响了体内向小球或肾小管衍生物的分化。

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