Karavanov A A, Karavanova I, Perantoni A, Dawid I B
Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Int J Dev Biol. 1998 Jan;42(1):61-6.
This study describes an in situ hybridization and immunohistochemical analysis of Lim-1 homeobox gene expression during kidney development in the rat. Lim-1 is expressed at all stages of mesonephric and metanephric kidney development. In the metanephros, Lim-1 gene mRNA is first found at day 13 in the ureteric bud, but not in uninduced mesenchyme. Expression in the mesenchyme can be seen only after mesenchymal cells have condensed around the ureteric bud tips and primary vesicles have formed. Experiments with mesenchymal explants induced to differentiate in vitro by high levels of basic FGF in the absence of ureteric bud also indicate that Lim-1 expression is correlated with tubulogenesis and this experimental model faithfully reproduces its expression in vivo. During mesenchymal differentiation Lim-1 protein and mRNA were found in comma- and S-shaped bodies, proximal and distal tubules, and collecting ducts. Lim-1 mRNA and Lim-1 protein were seen transiently at early stages of glomerulus formation. In the fully differentiated kidney Lim-1 gene products disappear from mesenchymal derivatives but persist in the collecting ducts which are derived from the ureteric bud. These data suggest a dual role for the Lim-1 homeobox gene in the developing kidney, a transient developmental function in the mesenchyme and a maintenance function in the ureteric bud and its derivatives. Further we suggest that Lim-1 is not directly involved in mesenchymal induction but may participate in its epithelial transformation at later stages as its expression in mesenchyme begins only after the formation of primary vesicle.
本研究描述了大鼠肾脏发育过程中Lim-1同源框基因表达的原位杂交和免疫组化分析。Lim-1在中肾和后肾发育的所有阶段均有表达。在后肾中,Lim-1基因mRNA于第13天首次在输尿管芽中发现,但在未诱导的间充质中未发现。只有在间充质细胞围绕输尿管芽尖凝聚并形成初级小泡后,才能在间充质中看到表达。在没有输尿管芽的情况下,用高水平碱性成纤维细胞生长因子诱导间充质外植体在体外分化的实验也表明,Lim-1表达与肾小管发生相关,并且该实验模型忠实地再现了其在体内的表达。在间充质分化过程中,Lim-1蛋白和mRNA在逗号状和S形小体、近端和远端小管以及集合管中被发现。在肾小球形成的早期阶段短暂地看到了Lim-1 mRNA和Lim-1蛋白。在完全分化的肾脏中,Lim-1基因产物从间充质衍生物中消失,但在源自输尿管芽的集合管中持续存在。这些数据表明Lim-1同源框基因在发育中的肾脏中具有双重作用,在间充质中具有短暂的发育功能,在输尿管芽及其衍生物中具有维持功能。此外,我们认为Lim-1不直接参与间充质诱导,但可能在后期参与其上皮转化,因为它在间充质中的表达仅在初级小泡形成后才开始。