Figure 7.

The proposed model for the regulation of ciliated cell differentiation by oxygen and Notch signaling. Submersion and/or hypoxia cause a low-oxygen environment that potentiates Notch signaling and prevents MCI and FOXJ1 expression, factors required for ciliated cell differentiation. Possible mechanisms for hypoxia potentiation of Notch signaling are indicated by the dashed arrow, and include induction of ligand expression, induction of Notch receptor expression, and direct interaction with NICD. Inhibition of γ-secretase with DAPT prevents Notch cleavage into the activated NICD form, and inhibits Notch signaling, which permits MCI and FOXJ1 expression and ciliated cell differentiation.