The essence of metazoa is the organization of cells into tissues. The most fundamental type of tissue is epithelia, which consist of a layer of polarized cells that line a surface and thus serve to divide the organism into compartments. Some epithelia cover the outside of the organism, but almost all metazoa contain internal hollow spaces or lumens, which are lined by a layer of epithelial cells. Such lumens may serve to isolate specific functions, such as digestion, or to allow the movement of fluids, gases or cells between different parts of larger animals. Some very small lumens are surrounded by a single cell, such as the terminal branches of the Drosophila
trachea, but most lumens are encompassed by multiple cells [1
]. The simplest overall structure of lumen-containing organs is a sphere, such as the thyroid follicle. Most typically, though, these organs are elongated into tubules, which can be unbranched (e.g. sweat gland) or branched, often ending in spherical caps, termed acini or alveoli (e.g. mammary gland or lung) [2
]. Some tubules form anastomosing networks, such as the vasculature, which is lined by specialized epithelia known as endothelia. All of these networks have in common a central lumen.
Lumens form during development by remarkably diverse mechanisms, including the wrapping, folding, invagination or evagination of polarized cell sheets to generate a hollow lumen [2
]. Loosely adherent mesenchymal cells can also convert into polarized epithelia, termed the mesenchymal–epithelialtransition [2
], and create lumens between the cells. Several reviews of tubule formation have described the molecular control of these processes in different organs [1
Certain common design principles underpin the seemingly enormous diversity of lumen and tubule formation mechanisms. In nearly all cases, lumens are lined by the apical surfaces of the limiting epithelial cells [3
]. (A fascinating variation is the circulatory system of certain invertebrates, which lacks endothelial cells and in which the basal surfaces of cells line the lumen, which is initially filled with extracellular matrix (ECM) [8
].) Formation of the apical surface involves the coordination of membrane trafficking machinery with the polarity complexes that define polarized plasma membrane domains [9
]. Moreover, in the case of multicellular lumens, cells must coordinate the orientation of their apical surfaces to face the lumen, which requires interaction of the cell with other cells and the ECM [10
What basic design principles are required for cells to form a lumen de novo? The first principle must involve cell–matrix and cell–cell recognition — sensing one’s environment and neighbors. This is a pre-requisite for determining where to form the lumen. The second principle must involve apical-basal polarization, spatiotemporally coordinated with neighboring cells. This can happen by one of at least three principal ways: hollowing, i.e. vectorial apical membrane transport to a common point between apposing cells, generating luminal space de novo; cavitation, i.e. clearing of non-ECM-contacting inner cells from a cell cluster, such as by apoptosis, resulting in a polarized layer surrounding luminal space;or focalized contact, where adjacent cells adhere only at their lateral-most apposing edges, generating luminal space between contacts (). A third design principle involves the expansion of the luminal space, such as by fluid and ion efflux. Here, we consider recent advances in our understanding of common design principles, across different species, tissues, and cells, of de novo lumen generation and expansion.
Design principles for de novo lumen formation