How to build an epithelial tree

Abstract

Nature has evolved a variety of mechanisms to build epithelial trees of diverse architectures within different organs and across species. Epithelial trees are elaborated through branch initiation and extension, and their morphogenesis ends with branch termination. Each of these steps of the branching process can be driven by the actions of epithelial cells themselves (epithelial-intrinsic mechanisms) or by the cells of their surrounding tissues (epithelial-extrinsic mechanisms). Here, we describe examples of how these mechanisms drive each stage of branching morphogenesis, drawing primarily on studies of the lung, kidney, salivary gland, mammary gland, and pancreas, all of which contain epithelial trees that form through collective cell behaviors. Much of our understanding of epithelial branching morphogenesis comes from experiments using mice, but we also include examples here from avian and reptilian models. Throughout, we highlight how distinct mechanisms are employed in different organs and species to build epithelial trees. We also highlight how similar morphogenetic motifs are used to carry out conserved developmental programs or repurposed to support novel ones. Understanding the unique strategies used by nature to build branched epithelia from across the tree of life can help to inspire creative solutions to problems in tissue engineering and regenerative medicine.

Contractile fibroblasts are recruited to the growing mammary epithelium to support branching morphogenesis

“…ECM expression and organization is another critical regulator of mammary epithelial branching [49][50][51] and our scRNAseq analysis reveals distinct patterns of ECM expression in different fibroblast clusters. Our analysis shows that peri-TEB fibroblasts express low levels of fibrillar collagens, including Col1a1 and Col1a2, suggesting that they may produce the collagen sheath only after their transition into peri-ductal fibroblasts.…”

Biomechanical regulation of cell shapes promotes branching morphogenesis of the ureteric bud epithelium

“…Extensive cell rearrangements and cell geometry changes sculpture epithelia in different developing organs across organisms ( 31 ). In essence, coordinated changes in the shapes of individual cells comprising the epithelium bend the tissue in a process leading to variations in morphological organization.…”

“…10,30 Extensive cell rearrangements and cell geometry changes sculpture epithelia in different developing organs across organisms. 31 In essence, coordinated changes in the shapes of individual cells comprising the epithelium bend the tissue in a process leading to variations in morphological organization. Highly dynamic cellular adhesions are intimately coupled to tightly regulated cell shape changes, which contribute to tissue remodeling and morphogenesis, as described in many developing organs in Drosophila.…”