A Self-Organizing miR-132/Ctbp2 Circuit Regulates Bimodal Notch Signals and Glial Progenitor Fate Choice during Spinal Cord Maturation

•miR-132 regulates Notch signaling and glial progenitor cell fate in spinal cord•The miR-132 target in this process is Ctbp2, controlling Notch signaling via Sirt1•A transient feedback loop between Ctbp2, Rest, and miR-132 induces miR-132•miR-132/Ctbp2 interplay in glial progenitors correlates with spinal cord maturation

SummaryRadial glial progenitors play pivotal roles in the development and patterning of the spinal cord, and their fate is controlled by Notch signaling. How Notch is shaped to regulate their crucial transition from expansion toward differentiation remains, however, unknown. miR-132 in the developing zebrafish dampens Notch signaling via a cascade involving the transcriptional corepressor Ctbp2 and the Notch suppressor Sirt1. At early embryonic stages, high Ctbp2 levels sustain Notch signaling and radial glial expansion and concomitantly induce miR-132 expression via a double-negative feedback loop involving Rest inhibition. The changing balance in miR-132 and Ctbp2 interaction gradually drives the switch in Notch output and radial glial progenitor fate as part of the larger developmental program involved in the transition from embryonic to larval spinal cord.

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