Parameters for stable Notch-independent Her6 oscillations across a frequency spectrum in neural stem cell populations
Neural proliferation zones drive the major growth phases of the vertebrate brain. Notch signaling and HES/Her transcription factors control neural stem cell (NSC) maintenance and neurogenesis, however the dynamic regulation of neural proliferation zones to sustain growth is not well understood. Notch-independent expression of the zebrafish HES1 homolog her6 in the larval brain is required for NSC maintenance and growth. We generated an mNeonGreen knock-in into the her6 locus and quantified Her6-mNeonGreen oscillations in vivo in distinct NSC populations. Her6 oscillates cell-autonomously across a broader frequency range, unaffected by inhibition of Notch signaling, and robustly reinitiated after experimental perturbations. Mathematical modelling reveals that Her6 oscillations prevail only when both transcript and protein degradation rate constants are equal. These intrinsic control parameters may have evolved to enable the Her6 oscillator to robustly maintain stemness during proliferative phases irrespective of local Notch signaling cues, and to provide for lineage stability while retaining plasticity for lineage progression.