Fusion of airways during avian lung development constitutes a novel mechanism for the formation of continuous lumena in multicellular epithelia

Abstract

Background: During development of the avian lung, the initially terminally branched epithelial tree later forms a continuous network of airways. This occurs via a large-scale epithelial fusion event, wherein airways that originate proximally collide with those that originate distally to form one continuous lumen. Results: Here, we found that prior to fusion, the epithelium of the embryonic chicken lung undergoes a shape change to permit the initiation and extension of new branches which contain the cells that initiate contact. These changes in epithelial shape coincide with the differentiation of smooth muscle cells that wrap the airways. From these nascent epithelial branches, individual cells form cytoskeletal protrusions that extend toward and form a bridge with their target airway. Additional cells then join the fusion site, forming a bilayered epithelium. During this process, the basement membrane around the prefusion epithelium degrades and then reforms after fusion. The epithelial bilayer then undergoes apoptosis, clearing the path between the two lumens. Conclusions: The process of airway epithelial fusion in the developing chicken lung constitutes a novel mechanism for the generation of complex multicellular tubes and suggests a conserved role for smooth muscle in the shaping of airway epithelia.

Bioassemblying Macro-Scale, Lumnized Airway Tubes of Defined Shape via Multi-Organoid Patterning and Fusion

“…Importantly, we discovered two critical fusion steps in MOA fusion and lumenization: inter-organoid surface integration and subsequent inner matter release. Interestingly, our findings showed great morphological similarities to selected in vivo epithelial tubulogenesis [34] . The establishment of inter-organoid envelopes in MOrPF mirrors the formation of protrusion-like fusion fronts between adjacent tubular branches in the embryonic Drosophila trachea [35] and chicken lung [34] .…”

“…Interestingly, our findings showed great morphological similarities to selected in vivo epithelial tubulogenesis [34] . The establishment of inter-organoid envelopes in MOrPF mirrors the formation of protrusion-like fusion fronts between adjacent tubular branches in the embryonic Drosophila trachea [35] and chicken lung [34] . The release of inner cell matter from MOAs may resemble cavitation (elimination of redundant cells from a solid-core tissue) in the developing Drosophila wing [36] and mouse salivary gland [37] .…”

Anatomy, variation, and asymmetry of the bronchial tree in the African grey parrot (Psittacus erithacus)

“…While the first two ventrobronchi and dorsobronchi exhibit similar distributions in all specimens, more distal secondary bronchi can differ in sequential number (e.g., in Figure 5f of “Euripides,” the left D7 and right D8), but occupy similar morphological positions in the lung. Recent findings in the developing avian lung found that the process by which parabronchial anastomoses form between secondary bronchial groups is, in contrast to the mammalian lung (Metzger et al, 2008), not developmentally stereotyped (Palmer & Nelson, 2020). The morphological variation of successive secondary bronchi seen here in adult lungs suggests that this lack of stereotypy may extend into the branching and distribution of larger secondary bronchi.…”

Won’t You be My Neighbor: How Epithelial Cells Connect Together to Build Global Tissue Polarity

“…While apical-to-apical epithelial fusion events are well-studied, recent investigations of development have revealed instances of basal-to-basal epithelial fusion ( Figure 1E ), including parabronchial fusion in chick lungs ( Palmer and Nelson, 2020 ), vertebrate optic fissure closure ( Chan et al, 2020 ), urogenital development ( Pyati et al, 2006 ; Chia et al, 2011 ; Slanchev et al, 2011 ; Weiss et al, 2014 ; Hoshi et al, 2018 ; Mello Santos and Hinton, 2019 ), and vertebrate mouth formation ( Soukup et al, 2013 ; Chen et al, 2017 ). This arrangement presents unique challenges including the barrier of the basement membrane between tissues and necessary polarity rearrangements upon fusion.…”

“…In mouse kidney development, loss of the basement membrane between the distal renal vesicle cells and the collecting duct is an early step in connecting these two epithelial tissues ( Georgas et al, 2009 ) ( Figure 2A ). In the chicken lung, anterior and posterior parabronchial tubules grow towards one another and fuse to form the continuous bronchial tubes required for respiration ( Palmer and Nelson, 2020 ), which involves basement membrane breakdown. Protrusive Wolffian Duct cells contact the cloacal lumen after basement membrane breakdown and then promote localized apoptosis to create the initial plumbing of the murine urogenital tract ( Hoshi et al, 2018 ).…”