Divide and polarize: recent advances in the molecular mechanism regulating epithelial tubulogenesis

Epithelial organs are generated from groups of non-polarized cells by a combination of processes that induce the acquisition of cell polarity, lumen formation, and the subsequent steps required for tubulogenesis. The subcellular mechanisms associated to these processes are still poorly understood. The extracellular environment provides a cue for the initial polarization, while cytoskeletal rearrangements build up the three-dimensional architecture that supports the central lumen. The proper orientation of cell division in the epithelium has been found to be required for the normal formation of the central lumen in epithelial morphogenesis. Moreover, recent data in cellular models and in vivo have shed light into the underlying mechanisms that connect the spindle orientation machinery with cell polarity. In addition, recent work has clarified the core molecular components of the vesicle trafficking machinery in epithelial morphogenesis, including Rab-GTPases and the Exocyst, as well as an increasing list of microtubule-binding and actin-binding proteins and motors, most of which are conserved from yeast to humans. In this review we will focus on the discussion of novel findings that have unveiled important clues for the mechanisms that regulate epithelial tubulogenesis.