Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance

  1. Mirjana Maletic-Savatic  Is a corresponding author
  2. Fatih Semerci
  3. William Tin-Shing Choi
  4. Aleksandar Bajic
  5. Aarohi Thakkar
  6. Juan Manuel Encinas
  7. Frederic Depreux
  8. Neil Segil
  9. Andrew K Groves
  1. Baylor College of Medicine, United States
  2. Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, United States
  3. Rosalind Franklin University of Medicine and Science, United States
  4. University of Southern California, United States

Abstract

Hippocampal neural stem cells (NSCs) integrate inputs from multiple sources to balance quiescence and activation. Notch signaling plays a key role during this process. Here, we report that Lunatic fringe (Lfng), a key modifier of the Notch receptor, is selectively expressed in NSCs, and that Lfng in NSCs along with Notch ligands Delta1 and Jagged1 expressed by their progeny influence NSC recruitment, cell cycle duration and terminal fate. We propose a new model in which Lfng-mediated Notch signaling enables direct communication between a NSC and its descendants, so that progeny can send feedback signals to the “mother” cell to modify its cell cycle status. Lfng-mediated Notch signaling appears to be a key factor governing NSC quiescence, division, and fate.

Article and author information

Author details

  1. Mirjana Maletic-Savatic

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    For correspondence
    maletics@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6548-4662
  2. Fatih Semerci

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0512-1827
  3. William Tin-Shing Choi

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Aleksandar Bajic

    Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Aarohi Thakkar

    Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Juan Manuel Encinas

    Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Frederic Depreux

    Department of Cell Biology and Anatomy, Rosalind Franklin University of Medicine and Science, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Neil Segil

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Andrew K Groves

    Program in Developmental Biology, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0784-7998

Funding

Cancer Prevention and Research Institute of Texas (RP130573CPRIT)

  • Mirjana Maletic-Savatic

Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD083092)

  • Mirjana Maletic-Savatic

National Center for Research Resources (S10RR024574)

  • Mirjana Maletic-Savatic

National Institute of Allergy and Infectious Diseases (AI036211)

  • Mirjana Maletic-Savatic

National Cancer Center (P30CA125123)

  • Mirjana Maletic-Savatic

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Elaine Fuchs, Howard Hughes Medical Institute, The Rockefeller University, United States

Ethics

Animal experimentation: Mouse studies were approved by the Baylor College of Medicine Institutional Animal Care and Use Committee.

Version history

  1. Received: December 24, 2016
  2. Accepted: July 11, 2017
  3. Accepted Manuscript published: July 12, 2017 (version 1)
  4. Accepted Manuscript updated: July 13, 2017 (version 2)
  5. Version of Record published: July 27, 2017 (version 3)

Copyright

© 2017, Maletic-Savatic 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. Mirjana Maletic-Savatic
  2. Fatih Semerci
  3. William Tin-Shing Choi
  4. Aleksandar Bajic
  5. Aarohi Thakkar
  6. Juan Manuel Encinas
  7. Frederic Depreux
  8. Neil Segil
  9. Andrew K Groves
(2017)
Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance
eLife 6:e24660.
https://doi.org/10.7554/eLife.24660

Share this article

https://doi.org/10.7554/eLife.24660

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