Notch signaling mediates olfactory multiciliated cell specification.

Epithelial multiciliated cells (MCCs) use motile cilia to direct external fluid flow, the disruption of which is associated with human diseases in a broad array of organs such as those in the respiratory, reproductive, and renal systems. While many of the signaling pathways that regulate MCC formation in these organ systems have been identified, similar characterization of MCC differentiation in the developing olfactory system has been lacking. Here, using live cell tracking, targeted cell ablation, and temporally-specific inhibition of the Notch signaling pathway, we identify the earliest time window of zebrafish olfactory MCC (OMCC) differentiation and demonstrate these cells' derivation from peridermal cells. We also describe regionally segregated Notch signaling across time points of rapid OMCC differentiation and show that Notch signaling downregulation yields an increase in OMCCs, suggesting that OMCC fate is normally repressed in a region-specific manner during olfactory development. Finally, we describe Notch signaling's regulation of the differentiation/ciliogenesis-associated genes foxj1a and foxj1b. Taken together, these findings provide new insights into the origins and developmental programming of OMCCs in vivo.