Figure 3: Notch signaling requirements in mucociliary cell types.

(A) Simplified schematic representation of the Notch pathway. Transmembrane Notch ligands from the Delta or Jagged families bind to transmembrane Notch receptors. Upon activation, Matrix metalloproteases (MMPs) cleave the extracellular portion of the complex, and γ-secretase cleaves off the Notch intracellular domain (NICD). NICD can then enter the nucleus, displace repressors from the RBPJ DNA-binding complex, and recruit transcriptional co-activators to initiate gene transcription. (B) Schematic representation of cell types in the mammalian trachea and their proposed requirement levels for active Notch signaling. Goblet, club cells and ionocytes show elevated Notch signaling, although at different levels, while MCCs and basal cells were proposed to be Notch independent. (C) Schematic representation of cell types in the Xenopus embryonic mucociliary epidermis and their proposed requirement levels for active Notch signaling. Basal and goblet cells show high Notch levels, and small secretory cells also require higher Notch levels for specification. Ionocytes and MCCs require low/no Notch signaling for specification and maintenance.