Cells into tubes: Molecular and physical principles underlying lumen formation in tubular organs

Tubular networks, such as the vascular and respiratory systems, transport liquids and gases in multicellular organisms. The basic units of these organs are tubes formed by single or multiple cells enclosing a luminal cavity. The formation and maintenance of correctly sized and shaped lumina are fundamental steps in organogenesis and are essential for organismal homeostasis. Therefore, understanding how cells generate, shape and maintain lumina is crucial for understanding normal organogenesis as well as the basis of pathological conditions. Lumen formation involves polarized membrane trafficking, cytoskeletal dynamics, and the influence of intracellular as well as extracellular mechanical forces, such as cortical tension, luminal pressure or blood flow. Various tissue culture and in vivo model systems, ranging from MDCK cell spheroids to tubular organs in worms, flies, fish, and mice, have provided many insights into the molecular and cellular mechanisms underlying lumenogenesis and revealed key factors that regulate the size and shape of cellular tubes. Moreover, the development of new experimental and imaging approaches enabled quantitative analyses of intracellular dynamics and allowed to assess the roles of cellular and tissue mechanics during tubulogenesis. However, how intracellular processes are coordinated and regulated across scales of biological organization to generate properly sized and shaped tubes is only beginning to be understood. Here, we review recent insights into the molecular, cellular and physical mechanisms underlying lumen formation during organogenesis. We discuss how these mechanisms control lumen formation in various model systems, with a special focus on the morphogenesis of tubular organs in Drosophila.