ESSENTIAL ROLE OF STROMAL MESENCHYME IN KIDNEY MORPHOGENESIS REVEALEDBY TARGETED DISRUPTION OF WINGED HELIX TRANSCRIPTION FACTOR BF-2

Metanephric mesenchyme gives rise to both the epithelial cells of the nephron and the stromal cells of the mature kidney. The function of th e stroma in kidney morphogenesis is poorly understood. We have generat ed mice with a null mutation in the Winged Helix (WH) transcription fa ctor BF-2 to examine its function during development. BF-2 expression within the developing kidney is restricted to the stromal cell lineage . Homozygotes die within the first 24 hr after birth with abnormal kid neys. Mutant kidneys are small, fused longitudinally, and rotated 90 d egrees ventrally. Histological examination reveals a smaller collectin g system, numerous large condensations of mesenchyme, and a decrease i n the number of nephrons. Using molecular markers we show that inducti on and condensation of the nephrogenic mesenchyme occurs normally in m utant. The disruption of BF-2 reduces the rate of differentiation of t he condensed mesenchyme into tubular epithelium, as well as the rate o f growth and branching of the ureter and collecting system. Our findin gs demonstrate that BF-2 and stromal cells have essential functions du ring kidney morphogenesis. Furthermore, they suggest that BF-2 control s the production, by the stroma, of signals or factors that are requir ed for the normal transition of induced mesenchyme into tubular epithe lium and full growth and branching of the collecting system.