Role of grainyhead-like 2 in the formation of functional tight junctions

Abstract

Epithelial cells develop intercellular junctions, including tight junctions (TJs) and adherens junctions (AJs). In epithelial tissues, TJs act as barriers that protect bodies from dehydration, infection and toxic substances. However, the molecular mechanisms regulating the establishment of functional TJs during organogenesis remain largely unknown. Recently, we identified grainyhead-like 2 (Grhl2) as a transcription factor that is specifically expressed in cholangiocytes, which are epithelial cells lining the bile duct tubules in the liver. Using our three-dimensional (3D) culture system of hepatic progenitor cells, we demonstrated that Grhl2 enhanced barrier functions of hepatic progenitor cells by upregulating claudin (Cldn) 3 and Cldn4, thereby promoting epithelial morphogenesis. In addition, we identified Rab25 as another target of Grhl2, which promotes the localization of Cldn4 at TJs. Our results indicate that a transcription factor promotes epithelial morphogenesis by establishing functional TJs by not only regulating the transcription of Cldns but also affecting their localization at TJs.