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. Further, Lfng in NSCs and Notch ligands Delta1 and Jagged1, expressed by their progeny, together 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.
Highlights
The ability of the hippocampal neurogenic niche to respond to ever-changing stimuli throughout the lifespan requires that it carefully maintain its finite stock of neural stem cells (NSCs) (Kuhn et al, 2005, 1996)
We demonstrate that Lunatic fringe (Lfng), a known regulator of Notch signaling, is selectively expressed in adult NSCs, where it participates in their preservation by regulating their cycling
We provide evidence that distinct modes of Notch signaling from NSC derivatives expressing Jag1 and Dll1 ligands, most likely mediated by Lfng, directly affect the NSC cell cycle
Summary
The ability of the hippocampal neurogenic niche to respond to ever-changing stimuli throughout the lifespan requires that it carefully maintain its finite stock of neural stem cells (NSCs) (Kuhn et al, 2005, 1996). NICD production increases upon binding by Delta-like (Dll) and decreases following Jagged (Jag1) binding (LeBon et al, 2014; Stanley and Okajima, 2010; Taylor et al, 2014; Yang et al, 2005); differential Notch cleavage ensures varying expression of downstream cell cycle genes (Chapouton et al, 2010; Isomura and Kageyama, 2014; Nellemann et al, 2001; Ninov et al, 2012; Yoshiura et al, 2007). Using several new transgenic mouse models, we unveil a novel Notch-based mechanism that mediates direct communication between NSCs and their progeny to control NSC quiescence and activation
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