Cao Mei, Liu Benchun, Cunha Gerald, Baskin Laurence
Department of Urology, University of California, San Francisco, California 94143, USA.
Pediatr Res. 2008 Oct;64(4):352-7. doi: 10.1203/PDR.0b013e318180e4c9.
Smooth muscle differentiation is induced in the embryonic bladder by the centrally located urothelium in the undifferentiated mesenchyme in the periphery adjacent to the serosa. We hypothesize that under the appropriate signal the entire undifferentiated bladder mesenchyme is capable of smooth muscle differentiation and that the urothelium patterns fibromuscular development. Embryonic bladders of wild-type and Green Fluorescent Protein mice were separated into urothelial and mesenchymal components before smooth muscle differentiation (E12.5-E13). The urothelial layer green fluorescent protein was recombined and grafted with the mesenchyme (wild-type) in an orthotopic position, heterotopic position and ectopic position. In all cases, a zone of smooth muscle inhibition was observed adjacent to the epithelium whether the urothelium was in an orthotopic or heterotypic position. Bladder mesenchyme and bladder epithelium grafted alone did not grow. In conclusion, the full thickness of bladder mesenchyme is capable of smooth muscle differentiation dependent on the location of urothelium. These experiments support the hypothesis that urothelium secretes a diffusible factor that at high concentrations inhibits smooth muscle and at low concentrations induces smooth muscle, thus patterning mesenchymal cell differentiation across the full thickness of the fibromuscular bladder wall.
在胚胎膀胱中，位于中央的尿路上皮可诱导其周边未分化间充质中的平滑肌分化，该未分化间充质毗邻浆膜。我们推测，在适当信号作用下，整个未分化膀胱间充质都有能力分化为平滑肌，且尿路上皮决定纤维肌发育模式。在平滑肌分化之前（胚胎第12.5天至13天），将野生型和绿色荧光蛋白小鼠的胚胎膀胱分离为尿路上皮和间充质成分。将尿路上皮层绿色荧光蛋白重组后，与间充质（野生型）原位、异位和异种移植。在所有情况下，无论尿路上皮处于原位还是异位，上皮附近均观察到平滑肌抑制区。单独移植膀胱间充质和膀胱上皮均未生长。总之，膀胱间充质全层能够分化为平滑肌，这取决于尿路上皮的位置。这些实验支持了这样的假说，即尿路上皮分泌一种可扩散因子，高浓度时抑制平滑肌，低浓度时诱导平滑肌，从而决定了纤维肌性膀胱壁全层间充质细胞的分化模式。
