Understanding how cells rearrange themselves into tissue structures is a main goal of developmental biology. Many structures rely on epithelial cells that line a lumen. For example, the tubular bile ducts of the liver are made of epithelial cells that both regulate the composition of bile and prevent leakage of bile along the tube. These epithelial cells are called cholangiocytes, and a recent paper paves the way towards understanding how these cells form the tube structures during development. In this paper, Senga and colleagues identified a transcription factor called grainyhead-like 2 (Grhl2) that regulates the size of a lumen surrounded by epithelial cells during development. Grhl2 upregulates claudin 3 and claudin 4, components of the tight junctions that provide a tight barrier between epithelial cells. Grhl2 also targets Rab25, which in turn increases claudin 4 levels and regulates its localization at tight junctions. As seen in the images above, expression of Grhl2 (bottom row) in cysts of liver progenitor cells causes rapid expansion of the lumen inside of the cysts without increasing the number of cells, compared with the slow formation of the lumen in a control cyst (top row).
Kazunori Senga, Keith E. Mostov, Toshihiro Mitaka, Atsushi Miyajima, & Naoki Tanimizu (2012). Grainyhead-like 2 regulates epithelial morphogenesis by establishing functional tight junctions through the organization of a molecular network among claudin3, claudin4, and Rab25 Molecular Biology of the Cell, 23 (15), 2845-2855 DOI: 10.1091/mbc.E12-02-0097
