Proper renal function relies on the tightly regulated development of nephrons and collecting ducts. This process, known as tubulogenesis, involves dynamic cellular and molecular changes that instruct cells to form highly organized tubes of epithelial cells which compartmentalize the renal interstitium and tubular lumen via assembly of a selective barrier. The integrity and diversity of the various renal epithelia is achieved via formation of intercellular protein complexes along the apical-basal axis of the epithelial cells. In recent years, the evolutionarily conserved family of Grainyhead-like (GRHL) transcription factors which encompasses three mammalian family members (Grainyhead-like 1, 2, 3) has emerged as a group of critical regulators for organ development, epithelial differentiation, and barrier formation. Evidence from transgenic animal models supports the presence of Grainyhead-like-dependent transcriptional mechanisms that promote formation and maintenance of epithelial barriers in the kidney. In this review, we highlight different Grhl-dependent mechanisms that modulate epithelial differentiation in the kidney. Additionally, we discuss how disruptions in these mechanisms result in impaired renal function later in life.
Keywords: Epithelial barrier; Epithelial morphogenesis; Grainyhead-like factors; Kidney development; Kidney disease; Tight junctions; Urothelial development.