Building branched tissue structures: from single cell guidance to coordinated construction

Abstract

Branched networks are ubiquitous throughout nature, particularly found in tissues that require large surface area within a restricted volume. Many tissues with a branched architecture, such as the vasculature, kidney, mammary gland, lung and nervous system, function to exchange fluids, gases and information throughout the body of an organism. The generation of branched tissues requires regulation of branch site specification, initiation and elongation. Branching events often require the coordination of many cells to build a tissue network for material exchange. Recent evidence has emerged suggesting that cell cooperativity scales with the number of cells actively contributing to branching events. Here, we compare mechanisms that regulate branching, focusing on how cell cohorts behave in a coordinated manner to build branched tissues. This article is part of the themed issue ‘Systems morphodynamics: understanding the development of tissue hardware’.

Paxillin-dependent regulation of apical-basal polarity in mammary gland morphogenesis

“…During ductal elongation, branching can be achieved through a combination of cell proliferation and cell rearrangement, involving bifurcation, where the ends of the duct split into two ducts and/or side branching of the main duct (Andrew and Ewald, 2010;Lu et al, 2008). Cell-extracellular matrix (ECM) adhesion signaling plays several key roles during these branching events, including further regulation of fibronectin turnover (Kadoya and Yamashina, 2010;Simian et al, 2001) as well as remodeling of the actin cytoskeleton to influence epithelial cell morphology, cell-cell interactions and cell motility (Spurlin and Nelson, 2017). F-actinassociated actomyosin contractility is also crucial for mammary gland branching morphogenesis.…”

Modeling branching morphogenesis using materials with programmable mechanical instabilities

“…Some general tissue characteristics that can determine the mode of branching morphogenesis include the presence of adjacent tissue layers (e.g., epithelium and mesenchyme) with distinct growth rates and compression ratios or the presentation of different types of gradients (e.g., ECM composition, cell differentiation) on the epithelial layer, which can potentially induce buckling and clefting morphogenesis, respectively. Moreover, the role of ubiquitous cell-cell and cell-ECM interactions is not conserved among different organs and modes of branching morphogenesis [54], despite the fact that their contributions affect tissue topology at different stages of morphogenesis [55]. …”

Stem cells in lung repair and regeneration: Current applications and future promise

“…For instance, the lung endoderm gives rise to at least four characteristically different epithelial regions. Each of these epithelial regions is composed with a different cell (Rock et al, ; Schittny, ; Spurlin & Nelson, ; Figure ). The lung structure also contains a variety of other cell types, including pulmonary neuroepithelial cells and bodies, and some hematopoietically‐derived cells such as mast cells, dendritic cells and macrophages.…”