Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.

Abstract:

:Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis.

journal_name

J Cell Biol

authors

Belicova L,Repnik U,Delpierre J,Gralinska E,Seifert S,Valenzuela JI,Morales-Navarrete HA,Franke C,Räägel H,Shcherbinina E,Prikazchikova T,Koteliansky V,Vingron M,Kalaidzidis YL,Zatsepin T,Zerial M

doi

10.1083/jcb.202103003

subject

Has Abstract

pub_date

2021-10-04 00:00:00

issue

10

eissn

0021-9525

issn

1540-8140

pii

212522

journal_volume

220

pub_type

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