In developing mammalian lungs, the terminal buds of elongating airways contain multipotent epithelial progenitors that give rise to the three major lung epithelial cell types: Clara, ciliated and neuroendocrine (NE) cells. Now, Mitsuru Morimoto and colleagues provide new insights into how Notch signalling regulates the distribution of these epithelial cell types in the airway (see p. ). Using stepwise removal of Notch1, Notch2 and Notch3 from developing mouse lung epithelium, the researchers show that Notch2 alone mediates the Clara/ciliated cell fate decision whereas all three receptors regulate NE fate selection in an additive manner. All three Notch receptors also additively regulate the size of the presumptive pulmonary neuroepithelial body (pNEB; NEBs are clusters of NE cells) through mutual interactions between NE cells and a population of SSEA-1 (stage-specific antigen 1)-positive epithelial cells that surrounds the pNEB. These and other results indicate that two different assemblies of Notch receptors control the number and distribution of lung epithelial cell types during lung organogenesis.
