Department of Chemical & Biological Engineering, Princeton University, Princeton, New Jersey, USA.
Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA.
Dev Dyn. 2020 Nov;249(11):1318-1333. doi: 10.1002/dvdy.215. Epub 2020 Jul 8.
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.
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.
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.
在禽类肺部发育过程中，最初末端分支的上皮树后来形成了连续的气道网络。这是通过大规模的上皮融合事件发生的，其中起源于近端的气道与起源于远端的气道碰撞，形成一个连续的腔。
在这里，我们发现融合之前，胚胎鸡肺的上皮经历了形状的变化，从而允许新分支的起始和延伸，这些分支包含启动接触的细胞。上皮形状的这些变化与包裹气道的平滑肌细胞的分化同时发生。从这些新生的上皮分支中，单个细胞形成细胞骨架突起，向其靶气道延伸并与之形成桥接。然后其他细胞加入融合部位，形成双层上皮。在此过程中，融合前上皮周围的基膜降解，融合后重新形成。上皮双层随后经历细胞凋亡，清除两个腔之间的通道。
发育中的鸡肺中的气道上皮融合过程构成了用于生成复杂的多细胞管的新机制，并提示平滑肌在气道上皮的形成中具有保守作用。
