ZINC FINGER PROTEINS IN EARLY KIDNEY DEVELOPMENT

后肾胚芽转化为肾后胚芽 通过移行输尿管芽上皮形成肾索。虽然有各种各样的 对这一过程中的形态事件进行了观测研究， 肾脏结构前转换的分子和生化基础 间充质尚不为人所知。涉及转分化的研究 肾干细胞进入成熟肾脏受到缺乏了解的限制。 产生信号通路的相互作用。很有可能采取的措施 向终末分化涉及蛋白质表达的变化 以及在发育中的肾单位周围，这样的变化可能是受控制的 到目前为止还没有被描述的基因。 我们假设决定图案形成的分子程序， 空间位置、细胞命运、表型和结构分化 由早期的一组主基因对形态发生线索做出反应来调节。 这个基因层级很可能是在转录控制之下 DNA结合基序的表达因素及这些蛋白的影响 对形成肾组织的命运的影响通过它们与 产生器官分化的其他下游基因。 在这个应用中，我们想要鉴定新的DNA结合蛋白 它们通过对转录的影响在肾脏发育中发挥作用。 我们认为分离和鉴定其中的几种是可行的 使用最受欢迎的基因方法的早期调控基因。有证据表明 锌指蛋白在肾单位发育中的重要性 在多个物种中从苍蝇往前飞。我们建议寻找其他新的 在胚胎小鼠肾脏中活跃的锌指。小鼠系统 如果人们想要研究高等脊椎动物，它提供了几个优势。多数 重要的是，我们希望确定一些基因的表型和功能 这些新的手指基因通过构建靶向突变作为重组 携带零等位基因的小鼠，最终，通过表征一些 它们与其他下游基因的相互作用。这样的信息将会有所帮助 为肾脏转录途径建立新的位置坐标 生长和成熟。

Metanephric blastema differentiates into kidney following conversion of the nephrogenic cord by migrating ureteric bud epithelium. While various morphologic events in this process have been studied observationally, the molecular and biochemical basis for the prestructural conversion of renal mesenchyme is not known. Studies that address the transdifferentiation of renal stem cells into mature kidney are limited by a lack of known interactions that create signaling pathways. It is quite likely that steps towards terminal differentiation involve changes in protein expression in and around developing nephrons, and such changes are probably controlled by as yet undescribed genes. We hypothesize that the molecular programs determining pattern formation, spatial position, cell fate, phenotype, and structural differentiation are regulated by early sets of master genes responding to morphogenic cues. This hierarchy of genes is probably under the control of transcription factors expressing DNA-binding motifs, and the influence of these proteins over the fate of forming renal tissue is mediated through their linkage to other downstream genes producing organ differentiation. In this application we would like to identify new DNA-binding proteins that play a role in kidney development by their effects on transcription. We believe it is feasible to isolate and characterize several of these early regulatory genes using a favorite gene approach. There is evidence for the importance of zinc finger proteins in the development of nephrons in multiple species from flies forward. We propose to look for other new zinc fingers that are active in embryonic murine kidney. The murine system offers several advantages if one wishes to study higher vertebrates. Most importantly, we expect to determine the phenotype and function of some of these new finger genes by constructing targeted mutations as recombinant mice carrying null alleles, and eventually, by characterizing some of their interactions with other downstream genes. Such information will help establish new positional coordinates for transcriptional pathways in renal growth and maturation.