Metanephros organogenesis is highly stimulated by vitamin A derivatives in organ culture.

Vitamin A and its metabolic derivatives are known to be key signalling molecules in regulating morphogenetic events in vertebrate development. Here we investigated their possible involvement during mammalian kidney development using paired rat metanephros organ culture. Metanephroi were explanted from 14-day-old embryos and cultured for six days in a chemically defined medium containing a retinoid at a dose of 10(-11) to 10(-4) M. Retinol, all-trans and 9-cis retinoic acid were able to promote metanephros growth and differentiation in vitro. A significant increase in the number of nephrons was observed from 10(-8) M of retinol and 10(-10) M of all-trans retinoic acid, before any change in growth parameters. A threefold increase in the number of nephrons was obtained at a dose of 10(-6) M. At low retinoid concentrations, there was a modulating effect of triiodothyronine on retinoid-stimulated nephrogenesis since the absence of triiodothyronine in the medium enhanced the nephrogenic stimulation. Exposure of metanephroi from 13-day-old embryos to all-trans retinoic acid (10(-7) M) led to a sixfold increase of nephron formation. Finally, we analyzed the branching pattern of the ureteric bud and showed that within 48 hours of culture, it was significantly more developed upon retinoid exposure. In conclusion, this study demonstrates that retinoic acid is a key regulator of renal organogenesis in controlling nephrogenic induction processes and ureteric bud patterning, and that the younger the metanephros, the greater the effect.