Understanding the mechanisms that regulate nephron progenitors during kidney development should aid development of therapies for renal failure. MicroRNAs, which modulate gene expression through post-transcriptional repression of specific target mRNAs, contribute to the differentiation of stem cells, but their role in nephrogenesis is incompletely understood. Here, we found that the loss of miRNAs in nephron progenitors results in a premature depletion of this population during kidney development. Increased apoptosis and expression of the pro-apoptotic protein Bim accompanied this depletion. Profiling of miRNA expression during nephrogenesis identified several highly expressed miRNAs (miR10a, miR-106b, miR-17-5p) in nephron progenitors that are either known or predicted to target Bim. We propose that modulation of apoptosis by miRNAs may determine congenital nephron endowment. Furthermore, our data implicate the pro-apoptotic protein Bim as a miRNA target in nephron progenitors. Kidney development begins with the outgrowth of the ureteric bud from the Wolffian duct into the metanephric mesenchyme. 1,2 The metanephric mesenchyme condenses as a tight "cap" of nephron progenitors around the tip of the ureteric bud and the ureteric bud branches to form the collecting system. Nephron progenitors have the capacity to selfrenew to generate the full complement of nephrons and to differentiate into the multiple cell types required to form the nephron. This process continues in an iterative fashion during nephrogenesis such that the most immature cells are present in the subcapsular cortex of the developing kidney, termed the nephrogenic zone.MicroRNAs (miRNAs) are a group of endogenous, small noncoding RNAs that function by causing the post-transcriptional repression of their respective target mRNAs. The first suggestion that miRNAs are critical in stem cell populations came from the observation that embryos that are null for Dicer, an enzyme required for the production of

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