Gene expression analysis of E16.5 Stk11-sufficient control and Sk11-/- lungs. Gene expression analysis of E16.5 Stk11-sufficient control and Sk11-/- lungs

Functional properties of mucosal surfaces are dependent on establishing the correct proportions of specialized epithelial cell types. In the mammalian airway, the proportions of ciliated and secretory cells types are tightly regulated to ensure efficient mucociliary clearance. Ciliated cells are one of the first mature cell types to be specified by differentiation of multipotent endodermal progenitors of the developing lung and can be replaced postnatally by differentiation of secretory progenitors. In each case, cell cycle exit is a necessary, early step that precedes differentiation. However, the relationship between cell cycle exit and cell fate determination is poorly understood. We show that the serine-threonine kinase Stk11 controls the cell cycle exit in airway stem/progenitor cells via phosphorylation and activation of the AMPK-related kinase Mark3, which directly suppresses Erk1/2 mediated Rb inactivation. Our study demonstrates that Stk11-dependent cell cycle exit accounts for the normal program of ciliated cell differentiation in developing and postnatal airways. Overall design: Examination of gene expression in two E16.5 Stk11-sufficient control lungs, examination of gene expression in two E16.5 Stk11-/- lungs.