Mah S P, Saueressig H, Goulding M, Kintner C, Dressler G R
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California, 92037, USA.
Dev Biol. 2000 Jul 1;223(1):38-53. doi: 10.1006/dbio.2000.9738.
During nephrogenesis, dynamic changes in the expression of cell adhesion molecules are evident as epithelial structures differentiate from the induced mesenchyme. The cadherins are thought to play an important role in the metanephric mesenchyme, when cells aggregate to form the renal vesicle, a polarized epithelial structure which eventually fuses with the ureteric bud to generate a continuous nascent nephron. We have generated and analyzed mice with a targeted mutation in the gene encoding cadherin-6 (Cad-6), a type II cadherin expressed during early stages of nephrogenesis. These mice are viable and fertile, and they complete both early and late aspects of nephrogenesis. However, upon closer examination in vitro and in vivo, a fraction of the induced metanephric mesenchyme in Cad-6 mutant kidneys fails to form a fully polarized epithelium on schedule. Moreover, a significant number of the renal vesicles in Cad-6 mutant kidneys apparently fail to fuse to the ureteric bud. These alterations in epithelialization and fusion apparently lead to a loss of nephrons in the adult. These studies support the idea that cadherins play an essential role in the formation of epithelial structures and underscore the importance of timing in orchestrating the morphogenesis of complex epithelial tissues.
在肾发生过程中，随着上皮结构从诱导的间充质分化而来，细胞黏附分子表达的动态变化十分明显。钙黏蛋白被认为在后肾间充质中发挥重要作用，此时细胞聚集形成肾小泡，这是一种极化的上皮结构，最终与输尿管芽融合以产生连续的新生肾单位。我们构建并分析了编码钙黏蛋白-6（Cad-6）的基因发生靶向突变的小鼠，Cad-6是一种在肾发生早期表达的II型钙黏蛋白。这些小鼠可存活且可育，它们完成了肾发生的早期和晚期过程。然而，在体外和体内进行更仔细的检查时，Cad-6突变体肾脏中一部分诱导的后肾间充质未能按时形成完全极化的上皮。此外，Cad-6突变体肾脏中大量的肾小泡显然未能与输尿管芽融合。上皮形成和融合的这些改变显然导致成年小鼠肾单位的丢失。这些研究支持了钙黏蛋白在形成上皮结构中起重要作用的观点，并强调了时间安排在协调复杂上皮组织形态发生中的重要性。
