Entrained pulmonary clocks: epithelium and vasculature keeping pace

a thin vascular-epithelial interface. Even minor problems in manufacture of this surface can cause air space hemorrhage in implanted tissue-engineered lung (10). Therefore, the ob-served spatiotemporal coordination of lung vascular and airway epithelial morphogenesis is welcome, if incompletely understood. Periodic airway branching depends on mesenchymal FGF-10 ligat-ing its epithelial receptor FGFR2b in concert with inducible negative regulator, Spry2 (14). By increasing intraluminal airway pressure, this clock can be sped up two- to threefold, resulting in shorter interbranch distances and more numer-ous, more tightly packed epithelial branches (13). This morphogenesis is set in the context of other periodic phe-nomena in prenatal lung that range from airway peristalsis, Ca2 waves, and fluid flux to fetal breathing movements (4, 6, 7). Alongside somite segmentation, lung branching an