Cloning and characterization of a novel gene promoting ureteric bud branching in the metanephros

Background. The ureteric buds and metanephric mesenchymal cells reciprocally induce each other's maturation during kidney development, and implicated transcription factors, secreted growth factors, and cell surface signaling peptides are critical regulators of renal branching morphogenesis. Protein kinase C (PKC) is a key enzyme in the signal transduction mechanisms in various biologic processes, including development, because it regulates growth and differentiation. Inhibition of PKC by the sphingolipid product ceramide interferes with nephron formation in the developing kidney, but the molecule that controls ureteric bud branching downstream of PKC is still unknown. Methods. Differential display polymerase chain reaction (PCR) of metanephroi cultured with a PKC activator and inhibitor was performed. We also examined the role of a novel gene in kidney development with organ culture system. Results. A novel gene encoding a 759 bp mRNA was identified, and we named it metanephros-derived tubulogenic factor (MTF)/L47. Inhibition of MTF with antisense oligonucleotide impaired ureteric bud branching by cultured metanephroi, and addition of recombinant MTF protein promoted ureteric bud branching in cultured metanephroi and increased cell proliferation. Conclusion. We identified a novel molecule in developing kidney that is capable of modulating ureteric bud branching and kidney differentiation.