Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.
Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.
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DOI：
10.1083/jcb.202103003
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发表时间：
2021-10-04
期刊：
影响因子：
--
通讯作者：
Zerial M
中科院分区：
文献类型：
--
作者：
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
Belicova等人。报告先前未被识别的顶膜延伸，形成一种使人联想到船的舱壁的图案，决定了肝细胞腔的各向异性扩张。Rab35沉默导致的舱壁丢失导致上皮极性和肝组织结构的重新设计。管腔形态发生是分子途径和机械力相互作用的结果。在几个器官中，上皮细胞共享它们的顶端表面，形成管腔。然而，在肝脏中，肝细胞仅在相邻细胞之间共享顶面，并形成各向异性生长的狭窄管腔，形成胆小管(BC)的3D网络。在这里，通过研究体外分化的小鼠肝母细胞的管腔形成，我们发现相邻的肝细胞组装了一种特定的顶膜延伸的模式，穿过管腔并确保其各向异性的扩张。这些以前未被识别的结构形成了一种模式，让人想起船只的舱壁，也存在于发育中的和成年的肝脏中。沉默Rab35导致心尖壁丧失和管腔各向异性，导致囊性形成。引人注目的是，我们可以在胚胎肝组织中重新设计肝细胞的极性，将BC转化为上皮管。我们的结果表明，顶壁是细胞固有的各向异性机械元件，在肝组织形态发生过程中决定了BC的伸长。
Belicova et al. report previously unrecognized apical membrane extensions, forming a pattern reminiscent of the bulkheads of boats, that determine the anisotropic expansion of hepatocyte lumina. Loss of the bulkheads caused by Rab35 silencing leads to re-engineering of epithelial polarity and liver tissue architecture. 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.
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影响因子：
46.9
作者：
Gilleron, Jerome;Querbes, William;Zerial, Marino
通讯作者：
Zerial, Marino
影响因子：
64.8
作者：
Dickinson ME;Flenniken AM;Ji X;Teboul L;Wong MD;White JK;Meehan TF;Weninger WJ;Westerberg H;Adissu H;Baker CN;Bower L;Brown JM;Caddle LB;Chiani F;Clary D;Cleak J;Daly MJ;Denegre JM;Doe B;Dolan ME;Edie SM;Fuchs H;Gailus-Durner V;Galli A;Gambadoro A;Gallegos J;Guo S;Horner NR;Hsu CW;Johnson SJ;Kalaga S;Keith LC;Lanoue L;Lawson TN;Lek M;Mark M;Marschall S;Mason J;McElwee ML;Newbigging S;Nutter LM;Peterson KA;Ramirez-Solis R;Rowland DJ;Ryder E;Samocha KE;Seavitt JR;Selloum M;Szoke-Kovacs Z;Tamura M;Trainor AG;Tudose I;Wakana S;Warren J;Wendling O;West DB;Wong L;Yoshiki A;International Mouse Phenotyping Consortium;Jackson Laboratory;Infrastructure Nationale PHENOMIN, Institut Clinique de la Souris (ICS);Charles River Laboratories;MRC Harwell;Toronto Centre for Phenogenomics;Wellcome Trust Sanger Institute;RIKEN BioResource Center;MacArthur DG;Tocchini-Valentini GP;Gao X;Flicek P;Bradley A;Skarnes WC;Justice MJ;Parkinson HE;Moore M;Wells S;Braun RE;Svenson KL;de Angelis MH;Herault Y;Mohun T;Mallon AM;Henkelman RM;Brown SD;Adams DJ;Lloyd KC;McKerlie C;Beaudet AL;Bućan M;Murray SA
通讯作者：
Murray SA
影响因子：
3.1
作者：
Grosse B;Degrouard J;Jaillard D;Cassio D
通讯作者：
Cassio D
影响因子：
25.7
作者：
Gissen P;Arias IM
通讯作者：
Arias IM
影响因子：
48
作者：
Franke, Christian;Sauer, Markus;van de Linde, Sebastian
通讯作者：
van de Linde, Sebastian