Open Accessβ-Catenin signaling dynamics regulate cell fate in differentiating neural stem cells
Author(s) -
Alyssa B. Rosenbloom,
Marcin Tarczyński,
Nora Lam,
Ravi S. Kane,
Lukasz J. Bugaj,
David V. Schaffer
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2008509117
Subject(s) - neural stem cell , cell fate determination , stem cell , microbiology and biotechnology , biology , optogenetics , catenin , wnt signaling pathway , cellular differentiation , signal transduction , neuroscience , genetics , transcription factor , gene
Stem cells undergo differentiation in complex and dynamic environments wherein instructive signals fluctuate on various timescales. Thus, cells must be equipped to properly respond to the timing of signals, for example, to distinguish sustained signaling from transient noise. However, how stem cells respond to dynamic variations in differentiation cues is not well characterized. Here, we use optogenetic activation of β-catenin signaling to probe the dynamic responses of differentiating adult neural stem cells (NSCs). We discover that, while elevated, sustained β-catenin activation sequentially promotes proliferation and differentiation, transient β-catenin induces apoptosis. Genetic perturbations revealed that the neurogenic/apoptotic fate switch was mediated through cell-cycle regulation by Growth Arrest and DNA Damage 45 gamma (Gadd45γ). Our results thus reveal a role for β-catenin dynamics in NSC fate decisions and may suggest a role for signal timing to minimize cell-fate errors, analogous to kinetic proofreading of stem-cell differentiation.