Quantitative modeling identifies critical cell mechanics driving bile duct lumen formation
Fig 9
Simulation results for Model 3, assuming Pl = 50Pa: Lumen area versus time.
(A) influence of cell-to-cell signalling times Tsig. (B) influence of absence or presence of Apical constriction (AC). The solid lines are the average of 5 stochastic realizations of the same parameter set, while the shadowed regions indicate the two times standard deviation interval of these realizations. An increase in lumen area from zero to ∼ 350μm2 in 24 hours is realistic since the area of lumina near the hilum ranged from 7 to 36 μm2 at E16.5 and from 116 to 674 μm2 at E18.5 (n = 10 at each stage) (C) Microscopic picture of small lumen with cholangiocytes (white arrowheads) and hepatoblasts (red arrowheads). Tissue section is stained to detect SOX9 (red), beta-catenin (green) and nuclei (DAPI, blue). (D) Snapshot of simulation showing a configuration comparable to that in panel C. The yellow arrows indicate the direction of cell-cell signalling during the formation.