The Function And Mechanism Of Nf1in Kidney Development

During kidney development， embryonic Six2-positive nephronprogenitor cells adjacent to ureteric bud tips ultimately give rise to nephronstructures, including proximal and distal tubules, podocytes, Bowman’scapsules, and the glomeruli. This process requires an internal balancebetween self-renew and differentiation of the nephron progenitor cells,which is mediated by numerous molecules（sush as: Six2, Sall1and Wnt4）.Nf1, containing2818aa, is a multifunctional protein widely expressed innumerous tissues including kidney, which is involved in several cellularpathways influencing morphogenetic processes and tumor formation.Recent studies have shown that the neurofibromin (Nf1) null mutant mouseembryos have an18-to24-h developmental delay in metanephrosmani-festing retardation in its cephalad repositioning and reduction numberof glomeruli. However, the underlying inter-/intra-cellular signalingmechanisms responsible for reducing number of glomeruli duringnephrogenesis remain to be fully elucidated. Here, we originally detectedthe Nf1expression in developing kidney and metanephric mesenchymecells. Surprisingly, Nf1knockdown by small interfering RNAs in the metanephric mesenchyme cells (mK3) resulted in a decreased expression ofSix2, the key marker of renal pro-genitor cells, while the ratio of apoptoticcells was significantly increased. Furthermore, overexpression ofSix2inmk3cells partially rescued apoptosis phenotype. Collectively, these resultsimplied that knockdown of Nf1resulted in apoptosis of mK3cells in vitroprobably through down-regulation of Six2expression. These resultsimplied that inhibition of Nf1may delay metanephros development viadown-regulation of Six2.