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

The following data sets were generated
    1. Werth et al.
    (2017) Identification of Tfcp2l1 target genes in the mouse kidney
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE87769).
    1. Werth M
    2. Barasch J
    (2017) Tfcp2l1 controls cellular patterning of the collecting duct.
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE85325).
    1. Werth M
    2. Barasch J
    (2017) Genome wide map of Tfcp2l1 binding sites from mouse kidney
    Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE87752).
The following previously published data sets were used

Article and author information

Author details

  1. Max Werth

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0169-6233
  2. Kai M Schmidt-Ott

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Thomas Leete

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Andong Qiu

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Christian Hinze

    Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Melanie Viltard

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Neal Paragas

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Carrie J Shawber

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Wenqiang Yu

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Peter Lee

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Xia Chen

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Abby Sarkar

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Weiyi Mu

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Alexander Rittenberg

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Chyuan-Sheng Lin

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Jan Kitajewski

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Qais Al-Awqati

    Columbia University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7141-1040
  18. Jonathan Barasch

    Columbia University, New York, United States
    For correspondence
    jmb4@columbia.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6723-9548

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.

Ethics

Animal experimentation: All experiments were approved by the Institutional Animal Care and Use Committee (IACUC) at Columbia. Protocol # AC-AAAH7404.

Reviewing Editor

  1. Roy Zent, Vanderbilt University Medical Center, United States

Version history

  1. Received: December 19, 2016
  2. Accepted: June 3, 2017
  3. Accepted Manuscript published: June 3, 2017 (version 1)
  4. Accepted Manuscript updated: June 13, 2017 (version 2)
  5. Version of Record published: June 26, 2017 (version 3)
  6. 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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  1. Max Werth
  2. Kai M Schmidt-Ott
  3. Thomas Leete
  4. Andong Qiu
  5. Christian Hinze
  6. Melanie Viltard
  7. Neal Paragas
  8. Carrie J Shawber
  9. Wenqiang Yu
  10. Peter Lee
  11. Xia Chen
  12. Abby Sarkar
  13. Weiyi Mu
  14. Alexander Rittenberg
  15. Chyuan-Sheng Lin
  16. Jan Kitajewski
  17. Qais Al-Awqati
  18. Jonathan Barasch
(2017)
Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts
eLife 6:e24265.
https://doi.org/10.7554/eLife.24265

Share this article

https://doi.org/10.7554/eLife.24265

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