Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts
- Columbia University, United States
- Max Delbruck Center for Molecular Medicine, Germany
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 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.
Data availability
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Identification of Tfcp2l1 target genes in the mouse kidneyPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87769).
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Tfcp2l1 controls cellular patterning of the collecting duct.Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE85325).
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RNA-Seq Gene Expression Analysis in Rat Metanephric Mesenchyme overexpressing Transcription Factor Tfcp2l1Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE87744).
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Genome wide map of Tfcp2l1 binding sites from mouse kidneyPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE87752).
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Mapping of transcription factor binding sites in mouse embryonic stem cellsPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE11431).
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Gene expression in epithelial and non-epithelial cells of renal originPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE24295).
Article and author information
Author details
Funding
National Institutes of Health (RO1DK073462)
- Jonathan Barasch
March of Dimes Foundation (Research Grant)
- Jonathan Barasch
National Institutes of Health (RO1DK092684)
- Jonathan Barasch
National Institutes of Health (U54DK104309)
- Jonathan Barasch
Deutsche Forschungsgemeinschaft (FOR 1368 FOR667 Emmy Noether)
- Kai M Schmidt-Ott
Urological Research Foundation Berlin
- Kai M Schmidt-Ott
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Roy Zent, Vanderbilt University Medical Center, United States
Ethics
Animal experimentation: All experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at Columbia. Protocol # AC-AAAH7404.
Version history
- Received: December 19, 2016
- Accepted: June 3, 2017
- Accepted Manuscript published: June 3, 2017 (version 1)
- Accepted Manuscript updated: June 13, 2017 (version 2)
- Version of Record published: June 26, 2017 (version 3)
- Version of Record updated: June 27, 2017 (version 4)
Copyright
© 2017, Werth et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts
eLife 6:e24265.
https://doi.org/10.7554/eLife.24265
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