1. Cell Biology
  2. Developmental Biology
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Transcription factor TFCP2L1 patterns cells in the mouse kidney collecting ducts

Research Article
  • Cited 25
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Cite this article as: eLife 2017;6:e24265 doi: 10.7554/eLife.24265

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 RO1DK092684)

  • Jonathan Barasch

March of Dimes Foundation (Research Grant)

  • Jonathan Barasch

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

Publication 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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Further reading

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    Sustained polarity and adhesion of epithelial cells is essential for the protection of our organs and bodies, and this epithelial integrity emerges during organ development amidst numerous programmed morphogenetic assaults. Using the developing C. elegans intestine as an in vivo model, we investigated how epithelia maintain their integrity through cell division and elongation to build a functional tube. Live-imaging revealed that apical PAR complex proteins PAR-6/Par6 and PKC-3/aPkc remained apical during mitosis while apical microtubules and microtubule-organizing center (MTOC) proteins were transiently removed. Intestine-specific depletion of PAR-6, PKC-3, and the aPkc regulator CDC-42/Cdc42 caused persistent gaps in the apical MTOC as well as in other apical and junctional proteins after cell division and in non-dividing cells that elongated. Upon hatching, gaps coincided with luminal constrictions that blocked food, and larvae arrested and died. Thus, the apical PAR complex maintains apical and junctional continuity to construct a functional intestinal tube.