Interaction between FGF and BMP signaling pathways regulates development of metanephric mesenchyme

Nephrogenesis in the mouse kidney begins at embryonic day 11 and ends simil ar to 10 days postpartum. During this period, new nephrons are continually being generated from a stem-cell population-the nephrogenic mesenchyme-in r esponse to signals emanating from the tips of the branching ureter. Relativ ely little is known about the mechanism by which the nephrogenic mesenchyme cell population is maintained at the tips of the ureter in the presence of signals promoting tubulogenesis. Previous studies have shown that a loss o f Bmp7 function leads to kidney defects that are a likely result of progres sive loss of nephrogenic mesenchyme by apoptosis. The studies presented her e demonstrate that BMP7 signaling can prevent apoptosis in explants of meta nephric mesenchyme. The surviving mesenchyme eel population, however, is no t competent to respond to signals promoting tubulogenesis. In conjunction w ith FGF2, BMP7 promotes growth and maintains competence of the mesenchyme i n vitro. In addition, FGF2 and BMP7 signaling, both independently and in co mbination, inhibit tubulogenesis. Interestingly, EGE2 and BMP7 also promote expansion of the stromal progenitor cell population in whole kidney cultur e. Because BMP7 is not produced by stromal progenitor cells, these data sug gest a novel interaction between the nephrogenic mesenchyme and stromal pro genitor cell populations. A model for the regulation of nephrogenesis by FG F and BMP signaling is presented.