ReviewTime to make the doughnuts: Building and shaping seamless tubes
Section snippets
What are seamless tubes?
Organs are composed of tubes with different sizes and shapes that are specialized for their particular functions [1]. Most tubes are composed of polarized epithelial or endothelial cells that have an apical surface facing the lumen and a basal surface facing other tissues, and that are linked together by adherens junctions and tight junctions. Branched organs, such as the mammalian vascular system, lung, and kidney, typically consist of centrally located, larger-bore tubes that transport fluids
Seamless tubes in the vertebrate vascular system
Unicellular seamed and seamless tubes make up a sizeable proportion of the capillaries in the vertebrate microvasculature. Decades ago, serial section transmission electron microscopy (TEM) studies of tissues from rats and other mammals revealed many capillaries with only a single cell surrounding the lumen [2], [9], [10]. Some such capillaries had an autocellular junction or “seam” that sealed the tube, but others had no darkly staining junctional material between the lumen and the plasma
Polarization
Seamless tube formation requires the cell to establish an unusual pattern of apical-basal polarity, with the apical domain inside the cell. The initial cues that establish such polarity are still unclear. Basal ECM factors may provide cues, since growing HUVEC cells in a 3D collagen matrix promotes intracellular lumen formation, and this requires integrin-ECM interactions [44]. Although integrins can affect terminal cell and canal tube shape [45], [46], they are not essential for polarization
Seamless tube shaping and maintenance
Seamless tubes exhibit varied shapes, including very elongated and branched shapes, as exemplified by terminal cells and the canal cell. The absence of junctions along seamless tubes presents special challenges for tube shaping and maintenance. In multicellular tubes and planar epithelia, junctions play important roles in polarity, trafficking, cytoskeletal organization and in generating and transmitting forces for tissue shaping [77], [78]. In seamless tubes, junctions are likely important
Summary and future challenges
Seamless tubes are found in many multicellular organisms, including mammals. The formation and maintenance of these tiny tubes present unique challenges. Recent studies in zebrafish, flies and worms have made great strides in visualizing the processes that build seamless tubes and in identifying specific genes required for their shaping and integrity. Cells can form seamless tubes through macropinocytosis, wrapping and auto-fusion, or apically directed exocytosis, but many questions remain
Acknowledgements
We thank Amin Ghabrial, John Murray, Janis Burkhardt and members of our laboratory for helpful discussions and comments on the manuscript. M.S. was supported by grants from NIH (R01GM58540) and NSF (1257879).
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