Columbia University, New York, United States; Max Delbruck Center for Molecular Medicine, Berlin, Germany; Department of Nephrology and Intensive Care Medicine, Charité - Universitaetsmedizin Berlin, Berlin, Germany
Thomas Leete
Columbia University, New York, United States
Andong Qiu
Columbia University, New York, United States; Tongji University, Shanghai, China
Christian Hinze
Max Delbruck Center for Molecular Medicine, Berlin, Germany
Melanie Viltard
Columbia University, New York, United States; Institute for European Expertise in Physiology, Paris, France
Neal Paragas
Columbia University, New York, United States; University of Washington, Seattle, United States
Carrie J Shawber
Columbia University, New York, United States
Wenqiang Yu
Columbia University, New York, United States; Fudan University, Shanghai, China
Peter Lee
Columbia University, New York, United States
Xia Chen
Columbia University, New York, United States
Abby Sarkar
Columbia University, New York, United States
Weiyi Mu
Columbia University, New York, United States
Alexander Rittenberg
Columbia University, New York, United States
Chyuan-Sheng Lin
Columbia University, New York, United States
Jan Kitajewski
Columbia University, New York, United States; University of Illinois at Chicago, Chicago, United States
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 Tfcp2l1 coordinates IC and PC development. Tfcp2l1 induces the expression of IC specific genes, including specific H+-ATPase subunits and Jag1. Jag1 in turn, initiates Notch signaling in PCs but inhibits Notch signaling in ICs. Tfcp2l1 inactivation deletes ICs, whereas Jag1 inactivation results in the forfeiture of discrete IC and PC identities. Thus, Tfcp2l1 is a critical regulator of IC-PC patterning, acting cell-autonomously in ICs, and non-cell-autonomously in PCs. As a result, Tfcp2l1 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.
