Bile – a fluid that aids digestion – is transported from the liver to the intestine through the bile duct. Bile reaches the bile duct itself via a complex, highly branched structure called the intrahepatic biliary network. This network spreads throughout the liver but how it is patterned is unclear. On p. 2595, Takuya Sakaguchi and colleagues report a novel computational approach to analyse the 3D structure of this network in developing zebrafish. They use a computational algorithm that renders confocal scans of labelled livers into compact representations of the intrahepatic biliary network, which recapitulate endogenous branching patterns and simplify the branched networks into segments amenable to further analysis. Using this computational approach, the authors identify a small molecule inhibitor of Cdk5 that reduces the density of the biliary network, leaving liver size and biliary epithelial cell numbers unchanged. They also experimentally manipulate the downstream Cdk5-Pak1-LimK-Cofilin cascade to increase branching density, and demonstrate a role for this cascade in regulating actin dynamics in biliary epithelial cells. These findings demonstrate the utility of this computational approach to studying branched tissues and highlight the Cdk5-Pak1-LimK-Cofilin cascade as a potential therapeutic target for liver disorders.
