URETERAL BUD CELLS SECRETE MULTIPLE FACTORS, INCLUDING BFGF, WHICH RESCUE RENAL PROGENITORS FROM APOPTOSIS

Kidney development requires reciprocal interactions between the ureter ic bud and the metanephrogenic mesenchyme. Whereas survival of mesench yme and development of nephrons from mesenchymal cells depends on sign als from the invading ureteric bud, growth of the ureteric bud depends on signals from the mesenchyme. This codependency makes it difficult to identify molecules expressed by the ureteric bud that regulate mese nchymal growth. To determine how the ureteric bud signals the mesenchy me, we previously isolated ureteric bud cell lines (UB cells). These c ells secrete soluble factors which rescue the mesenchyme from apoptosi s. We now report that four heparin binding factors mediate this growth activity. One of these is basic fibroblast growth factor (bFGF), whic h is synthesized by the ureteric bud when penetrating the mesenchyme. bFGF rescues three types of progenitors found in the mesenchyme: precu rsors of tubular epithelia, precursors of capillaries, and cells that regulate growth of the ureteric bud. These data suggest that the urete ric bud regulates the number of epithelia and vascular precursors that generate nephrons by secreting bFGF and other soluble factors.