Epithelial tissues are often associated with luminal structures. It is important to establish and maintain the appropriate size of the apical lumen during organogenesis. We have accessed molecular mechanisms promoting formation of the apical lumen and regulating the lumen size of bile ducts in the liver using three dimensional culture system of liver progenitor cells. We found that laminin isoforms, namely α1 chain-containing and α5 chain-containing laminins transmit signals to biliary epithelial cells (BECs) for establishing and maintaining the apical lumen, respectively (Tanimizu et al, JBC 2012). We identified grainyhead like-2 (Grhl2) as a BEC specific transcription factor, which enlarges the apical lumen of cysts derived from liver progenitor cells. We further demonstrated that Grhl2 contributes to formation of functional tight junctions by establishing the molecular network among claudin 3, 4 and Rab25, and thereby promotes epithelial morphogenesis (Senga et al. MBC 2012). Moreover, we found that Grhl2, which promotes structural maturation of epithelial tissues, limits lineage plasticity of BECs (Tanimizu et al. JCS 2013).