Stanniocalcin gene expression during mouse urogenital development: A possible role in mesenchymal-epithelial signalling

Abstract

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. © 2001 Wiley‐Liss, Inc.

Novel expression of the stanniocalcin gene in fish

“…Mammalian STC promotes phosphate reabsorption in both intestine and kidney, while inhibiting intestinal calcium uptake , Wagner et al 1997, Madsen et al 1998) both of which could serve to lower serum ionic calcium levels. In addition, STC expression is upregulated in neurons during cerebral ischemia (Zhang et al 2000), in MDCK cells during hypertonic stress (Sheikh-Hamad et al 2000), in human endothelial cells during differentiation (Kahn et al 2000) and during mammalian development (Stasko & Wagner 2001). Interestingly, STC only circulates in mammals during pregnancy (Deol et al 2000), suggesting that many of the reported effects are likely brought about by local hormone signaling through autocrine or paracrine pathways.…”

“…At the cellular level, low levels of STC mRNA and higher levels of irSTC protein were evident in most nephron segments (proximal I and II, distal tubule and collecting duct), similar to that found in mammals (Haddad et al 1996, Yoshiko & Maeda 1998. However, the highest levels of expression were observed in the cells of newly developing nephron segments, which is somewhat reminiscent of mammalian development where STC gene and protein activity are abundant in both metanephrogenic mesenchyme cells and developing ureteric bud (Stasko & Wagner 2001). Therefore, locally produced STC may have a role that is fundamental to the process of nephrogenesis in all vertebrates.…”

Characterization of Gene Expression Induced by RET with MEN2A or MEN2B Mutation

“…Moreover, the fact that the high STC1 expression was detected in ureteric bud/collecting duct cells of E14.5-18.5 mouse metanephric kidney and overlapped with RET expression at this stage suggests the possibility that STC1 expression and GDNF/RET signaling cooperatively function in kidney development. [3][4][5][6][57][58][59] Future studies will clarify the interesting roles of STC1 in the GDNF/RET signaling pathway as well as in tumor biology.…”

Mammalian stanniocalcins and cancer.

“…In a study of STC1 expression during mouse kidney development, STC1 was found to be produced by undifferentiated mesenchymal cells between embryonic days 10.5 and 14.5 and sequestered by non-expressing ureteric bud epithelial cells (Stasko & Wagner 2001b). This suggests that STC1 might have a role in mesenchymal-epithelial signaling.…”