Putting it Together: A Study of Epithelial Fusion in the Embryonic Avian Lung

Abstract

The structures of the lung and mechanisms of breathing of mammals and birds have several key differences which allow birds to fly at high altitudes. Air flow in mammals is bidirectional whereas air sacs in birds allow for unidirectional air flow. Bidirectional flow leads to the mixing of oxygen-rich and oxygen-poor air in the lung, thus lowering the maximum amount of oxygen that can diffuse into the blood. In avian lungs, parabronchi are arranged in parallel and ventilated on either end by secondary bronchi. Perfusion and ventilation occur perpendicular to each other and enable highly efficient gas exchange in avian lungs, which functions as a cross-current gas exchanger (Powell 2004). Mammalian lung airways end in cul-de-sacs, whereas in birds, fusion of the parabronchi allows for the formation of closed loops. Though only monopodial branching has been observed in the lungs of early (Hamburger-Hamilton stages 24 to 33, abbreviated as HH24 to HH33) chicken embryos (Gleghorn, Kwak et al. 2012), this study of older embryonic chicken lungs suggests that dichotomous branching also occurs in lungs at HH38 and HH38.5 just prior to epithelial fusion of the parabronchi. ! Increased expression of the transcription factor Slug and cleaved caspase-3 also suggests that mesenchymal cell death occurs prior to epithelial fusion. Preliminary EdU experiments also suggest that cell proliferation occurs diffusely around the area of fusion. These findings may contribute to the field of lung tissue engineering and the treatment of pulmonary diseases by increasing our understanding of the factors that control branching morphogenesis in the lung. Epithelial fusion and unidirectional air flow have also been noted in the lungs of reptiles including alligators and savannah monitor lizards. If the formation of their respiratory systems is governed by similar factors as those of birds, this may provide some insight as to when this characteristic airflow evolved.