Stasko S E, Wagner G F
Department of Physiology, Faculty of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Dev Dyn. 2001 Jan;220(1):49-59. doi: 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1086>3.0.CO;2-5.
Stanniocalcin (STC) is a polypeptide hormone first discovered in fish and more recently in mammals. In mammals, the STC gene is widely expressed and the hormone is involved in a variety of functions, but STC does not normally circulate in the blood. In both kidney and gut, STC regulates phosphate fluxes across the transporting epithelia, whereas in brain it protects neurons against cerebral ischemia and promotes neuronal cell differentiation. However, the gene is most highly expressed in ovary and expression is dramatically up-regulated by both pregnancy and nursing. STC mRNA levels are also high in the developing mouse embryo, but literally nothing is known of the tissue pattern of gene expression. Therefore, the aim of this study was to map the temporal and spatial patterns of gene expression during mouse embryologic development, starting with the urogenital system where the gene is so highly expressed in adults. STC mRNA was evident as early as E10.5 in both the mesonephros and genital ridge. Between E10.5 and 14.5 in developing kidney, STC was produced in undifferentiated mesenchyme cells and sequestered by ureteric bud epithelial cells that did not express the gene but nonetheless contained high levels of STC protein. Thereafter, the distribution pattern resembled that in adults such that gene expression predominated in collecting duct cells, whereas protein was present in most nephron segments. The pattern of gene expression during gonadal development was sexually dimorphic. In males, expression was first evident on E12.5 in interstitial mesenchyme cells surrounding the developing sex cords, whereas the protein accumulated in developing gonocytes within the sex cords that did not express the gene. This pattern became more pronounced over the course of gestation. In contrast, ovarian gene expression was only weakly evident during development. Collectively, the evidence suggests that in addition to its regulatory effects in adults, STC has novel and distinctive roles in the mesenchymal-epithelial interactions that are vital to normal organogenesis.
鲽源钙调蛋白（STC）是一种最初在鱼类中发现、最近在哺乳动物中也发现的多肽激素。在哺乳动物中，STC基因广泛表达，该激素参与多种功能，但STC通常不在血液中循环。在肾脏和肠道中，STC调节跨转运上皮的磷酸盐通量，而在大脑中，它保护神经元免受脑缺血并促进神经元细胞分化。然而，该基因在卵巢中表达最高，并且在妊娠和哺乳期间表达均显著上调。STC mRNA水平在发育中的小鼠胚胎中也很高，但对于基因表达的组织模式几乎一无所知。因此，本研究的目的是绘制小鼠胚胎发育过程中基因表达的时空模式，从该基因在成体中高表达的泌尿生殖系统开始。早在胚胎第10.5天，中肾和生殖嵴中就可明显检测到STC mRNA。在发育中的肾脏中，胚胎第10.5天至14.5天期间，STC由未分化的间充质细胞产生，并被输尿管芽上皮细胞隔离，这些上皮细胞不表达该基因，但却含有高水平的STC蛋白。此后，分布模式类似于成体，即基因表达在集合管细胞中占主导，而蛋白质存在于大多数肾单位节段中。性腺发育过程中的基因表达模式存在性别差异。在雄性中，胚胎第12.5天，在围绕发育中的性索的间质间充质细胞中首次明显检测到表达，而蛋白质在不表达该基因的性索内发育中的生殖细胞中积累。这种模式在妊娠过程中变得更加明显。相比之下，卵巢基因表达在发育过程中仅微弱可见。总体而言，证据表明，除了在成体中的调节作用外，STC在对正常器官发生至关重要的间充质 - 上皮相互作用中具有新的独特作用。
