Cho E A, Patterson L T, Brookhiser W T, Mah S, Kintner C, Dressler G R
Department of Pathology, University of Michigan, Ann Arbor, MI 48109-0650, USA.
Development. 1998 Mar;125(5):803-12. doi: 10.1242/dev.125.5.803.
The cadherin gene family encodes calcium-dependent adhesion molecules that promote homophilic interactions among cells. During embryogenesis, differential expression of cadherins can drive morphogenesis by stimulating cell aggregation, defining boundaries between groups of cells and promoting cell migration. In this report, the expression patterns of cadherins were examined by immunocytochemistry and in situ hybridization in the embryonic kidney, during the time when mesenchymal cells are phenotypically converted to epithelium and the pattern of the developing nephrons is established. At the time of mesenchymal induction, cadherin-11 is expressed in the mesenchyme but not in the ureteric bud epithelium, which expresses E-cadherin. The newly formed epithelium of the renal vesicle expresses E-cadherin near the ureteric bud tips and cadherin-6 more distally, suggesting that this primitive epithelium is already patterned with respect to progenitor cell types. In the s-shaped body, the cadherin expression patterns reflect the developmental fate of each region. The proximal tubule progenitors express cadherin-6, the distal tubule cells express E-cadherin, whereas the glomeruli express P-cadherin. Ultimately, cadherin-6 is down-regulated whereas E-cadherin expression remains in most, if not all, of the tubular epithelium. Antibodies generated against the extracellular domain of cadherin-6 inhibit aggregation of induced mesenchyme and the formation of mesenchyme-derived epithelium but do not disrupt ureteric bud branching in vitro. These data suggest that cadherin-6 function is required for the early aggregation of induced mesenchymal cells and their subsequent conversion to epithelium.
钙黏蛋白基因家族编码促进细胞间嗜同性相互作用的钙依赖性黏附分子。在胚胎发育过程中，钙黏蛋白的差异表达可通过刺激细胞聚集、界定细胞群之间的边界以及促进细胞迁移来驱动形态发生。在本报告中，通过免疫细胞化学和原位杂交技术，在胚胎肾中检查了钙黏蛋白的表达模式，此时间充质细胞在表型上转化为上皮细胞，并且发育中的肾单位模式得以建立。在间充质诱导时，钙黏蛋白-11在间充质中表达，但在表达E-钙黏蛋白的输尿管芽上皮中不表达。肾小泡新形成的上皮在输尿管芽尖端附近表达E-钙黏蛋白，在更远端表达钙黏蛋白-6，这表明这种原始上皮已经根据祖细胞类型形成了模式。在S形小体中，钙黏蛋白的表达模式反映了每个区域的发育命运。近端小管祖细胞表达钙黏蛋白-6，远端小管细胞表达E-钙黏蛋白，而肾小球表达P-钙黏蛋白。最终，钙黏蛋白-6被下调，而E-钙黏蛋白在大多数（如果不是全部）肾小管上皮中仍然表达。针对钙黏蛋白-6细胞外结构域产生的抗体可抑制诱导间充质的聚集和间充质来源上皮的形成，但在体外不会破坏输尿管芽的分支。这些数据表明，钙黏蛋白-6的功能对于诱导间充质细胞的早期聚集及其随后向上皮细胞的转化是必需的。
