Dicer function is essential for lung epithelium morphogenesis

摘要: DICER is a key enzyme that processes microRNA and small interfering RNA precursors into their short mature forms, enabling them to regulate gene expression. Only single Dicer exists in the mouse genome, it broadly expressed developing tissues. Dicer-null mutants die before gastrulation. Therefore, study function later event of lung formation, we inactivated epithelium using conditional allele Sonic Hedgehogcre (Shhcre) allele. Branching arrests these mutant lungs, although epithelial growth continues distal domains are expanded compared with normal samples. These defects result few large pouches instead numerous fine branches present lung. Significantly, initial phenotypes apparent an increase cell death observed, leading us propose plays specific role regulating morphogenesis independent its requirement survival. In addition, found expression Fgf10, involved development, up-regulated mesenchyme lungs. Previous studies support hypothesis precise localization FGF10 discrete sites serves as chemoattractant for outgrowth branches. The aberrant Fgf10 may contribute morphological defects. However, mechanism by which functions influence remains unknown.