Early restriction of peripheral and proximal cell lineages during formation of the lung

摘要

To establish the timing of lineage restriction among endodermal derivatives, we developed a method to label permanently subsets of lung precursor cells at defined times during development by using Cre recombinase to activate floxed alkaline phosphatase or green fluorescent protein genes under control of doxycycline- dependent surfactant protein C promoter. Extensive or complete labeling of peripheral lung, thyroid, and thymic epithelia, but not trachea, bronchi, or gastrointestinal tract occurred when mice were exposed to doxycycline from embryonic day (E) 4.5 to E6.5. Non- overlapping cell lineages of conducting airways (trachea and bron- chi), as distinct from those of peripheral airways (bronchioles, acini, and alveoli), were established well before formation of the defin- itive lung buds at E9-9.5.