The Role of Yap Signaling in Branching Morphogenesis and Cell-Fate Patterning in the Avian Lung

Abstract

Early embryonic avian lung development is regulated by a host of biochemical mechanisms and signaling pathways, many of which are conserved across species. The role of fibroblast growth factor (FGF), wingless integration site (WNT), and retinoic acid (RA) are well characterized within avian lung development, but little is known about the role of the Hippo pathway in branching morphogenesis in the avian lung. Here, we investigate the role of the Hippo pathway co-transcription factor Yes-associated protein (Yap) in avian lung development using immunostaining and microscopy to determine whether its function is conserved. We find that branch initiation is not accompanied by changes in the Yap signaling, suggesting that Yap does not drive the initial emergence of secondary bronchi. We also find that the spatial pattern of unphosphorylated, active Yap is dynamic across developmental time during branch elongation, from enrichment at distal tips at earlier time points to accumulation in regions of high epithelial cell density at later stages, suggesting a heterogeneous role in elongation. Furthermore, observed changes in Sox2 expression are not paralleled by changes in active Yap patterning, suggesting that Yap-driven transcription and Sox2-mediated cell fate patterning are regulated separately. Our investigation into the patterning of active Yap and Sox2 during chick lung development provides new insight into the role of Hippo signaling in branching morphogenesis in the avian lung.