The lmx1b gene is pivotal in glomus development in Xenopus laevis
The lmx1b gene is pivotal in glomus development in Xenopus laevis
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DOI：
10.1016/j.ydbio.2008.07.012
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发表时间：
2008-10-01
影响因子：
2.7
通讯作者：
Jones, Elizabeth A.
中科院分区：
文献类型：
--
作者：
Haldin, Caroline E.;Masse, Karine L.;Jones, Elizabeth A.
我们之前已经证明 lmx1b（一种 LIM 同源域蛋白）在前肾球中表达。我们现在展示了 lmx1b 及其潜在结合伴侣在解剖的原肾原基和 42 期原肾的单个解剖成分中的时间和空间表达模式。 lmx1b 的吗啡寡核苷酸敲低确立了 lmx1b 在前肾成分发育中的作用。 lmxlb 的消耗导致形成尺寸减小的球团。前肾小管的结构和/或卷曲也减少，而更远端的肾小管结构不受影响。 lmx1b mRNA 的过度表达没有导致显着的表型。鉴于已知 lmx1b 蛋白以异二聚体的形式发挥作用，我们单独或与潜在的相互作用分子结合过表达 lmx1b mRNA，并分析了其对肾脏结构的影响。通过与 lmxlb mRNA 共注射可以部分挽救通过 lim1 和 ldb1 过表达观察到的表型。动物帽实验证实，lmx1b 与潜在结合伴侣的共注射可以上调前肾分子市场，表明 lmx1b 位于控制血管球分化的基因网络中 wt1 的上游。这将 lmx1b 置于参与原肾发育的遗传层次中，并表明结合配偶体水平的平衡以及 lmx1b 和 lim1 的限制性表达域影响了体内向血管球或小管衍生物的分化。 (c) 2008 Elsevier Inc. 保留所有权利。
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 lmxlb 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 overexpression of lim1 and ldb1 are partially rescued by co-injection with lmxlb mRNA. Animal cap experiments confirm that co-injection of lmx1b with potential binding partners can up-regulate pronephric molecular markets 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. (c) 2008 Elsevier Inc. All rights reserved.