Fig. 10: A model of lung branching and saccule formation.

a Schematic diagram of lung branching and saccule formation in control lungs. The conducting airways extend from the trachea and main stem bronchi. A signaling cascade that involves mTORC1 (Rptor) signaling, mitochondrial capacity (Tfam and Cox10) and Hedgehog (Hh) signaling controls lung branching to form the conducting airways. Saccules are subsequently generated at the end of the conducting airways. Production of the conducting airways and saccules is also closely associated with proper cell differentiation. b Schematic diagram of lung branching and saccule formation in lungs with disrupted mTORC1 signaling, reduced mitochondrial capacity or perturbed Hedgehog (Hh) signaling. In these mutants, the conducting airways are missing and are replaced by lung cysts. Saccule-like structures form on the cystic surface. This suggests that distinct programs control lung branching and saccule formation. It also indicates the presence of a developmental clock that controls lung development.