Lunatic fringe-mediated Notch signaling regulates adult hippocampal neural stem cell maintenance
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.
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Author details
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
- 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
- Received: December 24, 2016
- Accepted: July 11, 2017
- Accepted Manuscript published: July 12, 2017 (version 1)
- Accepted Manuscript updated: July 13, 2017 (version 2)
- 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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