The fate of Notch-deficient nephrogenic progenitor cells during metanephric kidney development

摘要: To determine which nephron segments require Notch signals for development, we conditionally deleted Rbpj , a transcription factor required canonical signaling, in nephrogenic progenitors (NPs) of the metanephric mesenchyme. The retinoic acid receptor-β2 (Rarb2) promoter efficiently directed Cre-recombinase (Cre) activity to these progenitors. Conditional knockout mice (Rarb2Cre + / f/− ) caused severe renal hypoplasia, as indicated by 70–95% reduction number and development tubular cysts. track fate NPs following Rarb2Cre expression, labeled them with membrane-associated enhanced green fluorescent protein (GFP). In TomatoGFP /Rarb2Cre control mice, differentiated into epithelia all segments, except collecting ducts. /Rbpj conditional developed podocytes or distal epithelia, indicating that were not mesenchymal-to-epithelial transition specification segments. Conversely, few proximal tubules associated cysts derived from 5–10% had failed express Cre and, therefore, intact signaling. Thus, our mapping studies establish profound effect signaling on nephrogenesis is due but podocytes.