Unexpected features of tubologenesis. How hepatocytes turn spherical lumens into elongated tubes.
Lumenogenesis is a common mechanism in plant and animals that consists in creating, gaps, and lumens between cells to allow the formation of ducts. The creation of tubes occurs following several scenarios that are worth comparing. In this presentation I will present our understanding of how small canaliculi are formed by hepatocytes in livers. These canaliculi collect the secreted bile and their morphogenesis is very poorly understood. Deficient formation leads defects in bile flows and consequently diseases (cholestasis). We adopted a deconstrutivist approach to understand how an osmotically driven growth of canaliculi can anisotropically lead to the development of a tube. I will show how single hepatocytes (the main cellular constituents of the liver) can be induced to form spherical hemi-lumen by contact with an inert material, demonstrating that lumenogenesis initiation does not require the concomitant development of lumen in the neighboring cells. I will then show how the spatial geometry of extra cellular matrix provides a guidance tool to favor the development of tubulogenesis in the direction of lowest intra-cellular tension. Lastly, I will show the existence of special protrusions crossing the lumen cavity, bridging, suturing, the developing lumen to putatively minimize its extension in the lateral direction, and consequently favoring its extension along the tubular axis.
 Zhang, Y. et al. Biomimetic niches reveal the minimal cues to trigger apical lumen formation in single hepatocytes. Nat Mater, doi:10.1038/s41563-020-0662-3 (2020).
 Li, Q. et al. Extracellular matrix scaffolding guides lumen elongation by inducing anisotropic intercellular mechanical tension. Nat Cell Biol 18, 311-318, doi:10.1038/ncb3310 (2016).
 Stoecklin, C. et al. A New Approach to Design Artificial 3D Microniches with Combined Chemical, Topographical, and Rheological Cues. Advanced Biosystems 0, 1700237, doi:doi:10.1002/adbi.201700237 (2018).
 Dasgupta, S., Gupta, K., Zhang, Y., Viasnoff, V. & Prost, J. Physics of lumen growth. Proc Natl Acad Sci U S A 115, E4751-E4757, doi:10.1073/pnas.1722154115 (2018).
CNRS and Mechanobiology Institute of Singapore