Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts

Abstract

Although most nephron segments contain one type of epithelial cell, the collecting ducts consists of at least two: intercalated (IC) and principal (PC) cells, which regulate acid-base and salt-water homeostasis, respectively. In adult kidneys, these cells are organized in rosettes suggesting functional interactions. Genetic studies in mouse revealed that transcription factor <i>Tfcp2l1</i> coordinates IC and PC development. <i>Tfcp2l1</i> induces the expression of IC specific genes, including specific H⁺-ATPase subunits and <i>Jag1. Jag1</i> in turn, initiates Notch signaling in PCs but inhibits Notch signaling in ICs. <i>Tfcp2l1</i> inactivation deletes ICs, whereas <i>Jag1</i> inactivation results in the forfeiture of discrete IC and PC identities. Thus, <i>Tfcp2l1</i> is a critical regulator of IC-PC patterning, acting cell-autonomously in ICs, and non-cell-autonomously in PCs. As a result, <i>Tfcp2l1</i> regulates the diversification of cell types which is the central characteristic of 'salt and pepper' epithelia and distinguishes the collecting duct from all other nephron segments.