Vainio S J, Uusitalo M S
University of Oulu, Department of Biochemistry, Linnanmaa, Finland.
Pediatr Nephrol. 2000 Nov;15(1-2):151-6. doi: 10.1007/s004670000404.
Classical in vitro studies indicate that tubule induction in the kidney mesenchyme is mediated by cell-cell contacts between the inducer tissue and the metanephric mesenchyme. Induction is completed within the first 24 h, after which tubules will form because of stimulated cell proliferation, migration, and cell adhesion. Recent evidence has revealed an essential role for the secreted signals from the Wnt gene family. Of these, Wnt-4 is expressed in developing tubules and knocking out its function perturbed kidney development. More detailed studies demonstrated normal condensation, but tubules were missing. Subsequent experiments indicated that Wnt-4 is also a sufficient signal to trigger tubulogenesis. Cells that were engineered to express Wnt-4 not only induced tubulogenesis in the kidney mesenchyme of Wnt-4 mutant embryos, but also induced tubules in the wild type mesenchyme. With the transfilter induction assay, Wnt-4-mediated induction was completed within the first 24 h, depending on the presence of proteoglycans and cell-cell contacts between the interactants. In addition, Wnt-4 autoinduced expression of its own gene and a panel of other components of the Wnt signalling pathway, such as frizzleds and a candidate Wnt antagonist from the secreted frizzled-related protein family. Taken together, the data provide evidence of an essential role for Wnt signal transmission and transduction pathways in the induction of kidney tubules, and the findings have paved the way for detailed molecular studies.
经典的体外研究表明，肾间充质中的肾小管诱导是由诱导组织与后肾间充质之间的细胞间接触介导的。诱导在最初的24小时内完成，之后由于刺激的细胞增殖、迁移和细胞黏附，肾小管将形成。最近的证据揭示了Wnt基因家族分泌信号的重要作用。其中，Wnt-4在发育中的肾小管中表达，敲除其功能会干扰肾脏发育。更详细的研究表明，凝聚正常，但肾小管缺失。随后的实验表明，Wnt-4也是触发肾小管形成的充分信号。经基因工程改造以表达Wnt-4的细胞不仅在Wnt-4突变胚胎的肾间充质中诱导了肾小管形成，而且在野生型间充质中也诱导了肾小管。通过跨滤器诱导试验，Wnt-4介导的诱导在最初的24小时内完成，这取决于蛋白聚糖的存在以及相互作用物之间的细胞间接触。此外，Wnt-4自身诱导其自身基因以及Wnt信号通路的一组其他成分的表达，如卷曲蛋白和来自分泌型卷曲相关蛋白家族的一种候选Wnt拮抗剂。综上所述，这些数据提供了证据，证明Wnt信号传递和转导通路在肾小管诱导中起重要作用，这些发现为详细的分子研究铺平了道路。
