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Unlike most epithelial cells, hepatocytes express both E- and N-cadherin, yet their specific roles during BC tubulogenesis remain incompletely understood. Here, we show that these cadherins are collectively required for hepatic polarity and BC formation yet act through distinct mechanisms. E-cadherin localizes to adherens junctions, lateral membranes, and the cleavage furrow, where it promotes division-linked BC elongation and cell\u2013cell contact formation by controlling spindle orientation and RhoA activation via NuMA and ARHGEF17. In contrast, N-cadherin is restricted to adherens junctions and maintains hepatic polarity by attenuating RhoA activity through the p120-catenin family member ARVCF and its partner p190B\/ARHGAP5. Together, these findings reveal that dual cadherin expression drives hepatic polarity and BC formation by controlling RhoA activity in a coordinated yet opposing manner.<\/jats:p>","DOI":"10.1083\/jcb.202509170","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:21:11Z","timestamp":1777616471000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9974-3696","authenticated-orcid":true,"given":"Junya","family":"Hayase","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Cell and Developmental Biology, , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5227-9041","authenticated-orcid":true,"given":"Li","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0106qb496","id-type":"ROR","asserted-by":"publisher"}],"name":"State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Institutes of Biomedical Sciences, Inner Mongolia University 2 , Hohhot,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1118-7582","authenticated-orcid":true,"given":"Yu-Heng","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Basic Medical Sciences, Peking University 3 State Key Laboratory of Female Fertility Promotion, Department of Medical Genetics, , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-9989","authenticated-orcid":true,"given":"Kangji","family":"Wang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Cell and Developmental Biology, , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0583-4464","authenticated-orcid":true,"given":"Cheng-Ran","family":"Xu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Basic Medical Sciences, Peking University 3 State Key Laboratory of Female Fertility Promotion, Department of Medical Genetics, , Beijing,","place":["China"]},{"id":[{"id":"https:\/\/ror.org\/02v51f717","id-type":"ROR","asserted-by":"publisher"}],"name":"Peking-Tsinghua Center for Life Sciences, Peking University 4 , Beijing,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-3608","authenticated-orcid":true,"given":"Erfei","family":"Bi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00b30xv10","id-type":"ROR","asserted-by":"publisher"}],"name":"Perelman School of Medicine, University of Pennsylvania 1 Department of Cell and Developmental Biology, , Philadelphia, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"2026052812172795600_bib1","doi-asserted-by":"publisher","first-page":"8419","DOI":"10.1073\/pnas.0600246103","article-title":"Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver","volume":"103","author":"Battle","year":"2006","journal-title":"Proc. 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