Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads

Abstract:

Lumen morphogenesis is key to the function of organs and results from the integration of molecular pathways and mechanical forces1–3. The mechanisms governing anisotropic lumen expansion remain elusive4–6. In contrast to epithelial cells which have simple apico-basal polarity and form tubes, hepatocytes are multi-polar and form narrow lumina that grow anisotropically between adjacent cells, collectively generating a complex 3D network of bile canaliculi (BC)7,8. Here, we studied lumen elongation and BC morphogenesis in differentiating primary mouse hepatoblasts in vitro. Remarkably, we discovered a pattern of specific extensions of the apical membrane traversing the lumen between adjacent hepatocytes and sealed by tight junctions, reminiscent of the bulkheads of boats. These structures were also present in the developing liver. A targeted screen revealed that silencing of Rab35 caused loss of the bulkheads, conversion of hepatocyte into simple epithelial polarity and formation of spherical lumina in vitro. Strikingly, we could re-engineer hepatocyte polarity and tissue morphogenesis in vivo in the embryonic liver, converting BC into simple epithelial tubes. Our results suggest that the apical bulkheads of hepatocytes are cell-intrinsic anisotropic mechanical elements that ensure stability of the elongating lumen between two cells, thus determining the structure of BC during liver tissue morphogenesis.

Citation: biorxiv;2020.12.31.424978v2,[Preprint]

Date Published: 2021

Registered Mode: by DOI

Authors: Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, José Ignacio Valenzuela, Hernán Andrés Morales-Navarrete, Christian Franke, Helin Räägel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis Kalaidzidis, Timofei Zatsepin, Marino Zerial

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Belicova, L., Repnik, U., Delpierre, J., Gralinska, E., Seifert, S., Ignacio Valenzuela, J., Morales-Navarrete, H. A., Franke, C., Räägel, H., Shcherbinina, E., Prikazchikova, T., Koteliansky, V., Vingron, M., Kalaidzidis, Y., Zatsepin, T., & Zerial, M. (2021). Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads. In []. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.12.31.424978
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Created: 25th Jun 2021 at 09:52

Last updated: 8th Mar 2024 at 07:44

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