E- and N-cadherin drive hepatic polarity and lumen elongation via opposing effects on RhoA activity.

Hepatocytes display a unique polarity, forming narrow apical tubes-bile canaliculi (BCs)-between adjacent cells that are essential for liver function. 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-cell 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.