Termination of cell-type specification gene programs by the miR-183 cluster determines the population sizes of...

Touch and mechanical sensations require the development of several different kinds of sensory neurons dedicated to respond to certain types of mechanical stimuli. The transcription factor Shox2 (short stature homeobox 2) is involved in the generation of TRKB⁺ low-threshold mechanoreceptors (LTMRs), but mechanisms terminating this program and allowing alternative fates are unknown. Here, we show that the conditional loss of the miR-183-96-182 cluster in mouse leads to a failure of extinction of Shox2 during development and an increase in the proportion of Aδ LTMRs (TRKB⁺/NECAB2⁺) neurons at the expense of Aβ slowly adapting (SA)-LTMRs (TRKC⁺/Runx3^-) neurons. Conversely, overexpression of miR-183 cluster that represses Shox2 expression, or loss of Shox2, both increase the Aβ SA-LTMRs population at the expense of Aδ LTMRs. Our results suggest that the miR-183 cluster determines the timing of Shox2 expression by direct targeting during development, and through this determines the population sizes of Aδ LTMRs and Aβ SA-LTMRs.