Figure 4. Proximal airway development is unaffected by loss of YAP in the distal airway.
(A–H) Immunostaining of lung sections collected from wild-type, Yapf/f; Sox9Cre/+ and Yapf/f; spcCre/+ mice at 14.5 and 18.5 dpc as indicated. Proximal-distal airway specification was unaffected in Yapf/f; Sox9Cre/+ lungs as revealed by proper expression of the proximal (SOX2) and distal (SOX9) airway markers despite cyst formation in the SOX9+ lung epithelium. Moreover, cell types in the proximal airway of Yapf/f; Sox9Cre/+ and Yapf/f; spcCre/+ mice were specified. For example, cells expressing CC10 (Clara cell marker) and acetylated-tubulin [Ac-tub] (ciliated cell marker) were detected in a similar pattern between control and mutant lungs. Scale bar = 100 μm for A–H.
Figure 4—figure supplement 1. Disruption of the distal airway in Yapf/f; spcCre/+ and Yapf/f; Sox9Cre/+ mouse lungs.
(A–H) Immunostaining of lung sections collected from wild-type, Yapf/f; spcCre/+ and Yapf/f; Sox9Cre/+ mice at 12.5 and 18.5 days post coitus (dpc) as indicated. Lung cysts were detected in the distal airway of Yapf/f; spcCre/+ and Yapf/f; Sox9Cre/+ mice. Cell types in the proximal airway of Yapf/f; spcCre/+ and Yapf/f; Sox9Cre/+ mice appeared to be properly specified as indicated by their expression of CC10 (Clara cell marker) and acetylated-tubulin [Ac-tub] (ciliated cell marker). SOX2 expression, which marks the proximal airway, was detected in a localized region of the lung cyst in Yapf/f; spcCre/+ mice at 12.5 dpc. This suggests that while lung branching morphogenesis was disrupted in Yapf/f; spcCre/+ lungs, specification of the proximal-distal airway was unaffected. Scale bar = 50 μm for A, E; 100 μm for B–D, F–H.