GemC1 governs multiciliogenesis through direct interaction and transcriptional regulation of p73

A distinct combination of transcription factors elicits the acquisition of a specific fate and the initiation of a differentiation program. Multiciliated cells are a specialized type of epithelial cells that possess dozens of motile cilia on their apical surface. Defects in cilia function have been associated with ciliopathies that affect many organs, including brain and airway epithelium. Here we show that GemC1/Lynkeas regulates the transcriptional activation of p73, a transcription factor central to multiciliogenesis. Moreover, we show that GemC1/Lynkeas acts in a trimeric complex with E2F5 and p73 and that this complex is important for the activation of the p73 promoter. We also provide in vivo evidence that GemC1/Lynkeas is necessary for p73 expression in different multiciliated epithelia. We further show that GemC1/Lynkeas regulates multiciliogenesis through the control of chromatin organization and epigenetic marks of p73 and FoxJ1. Our results highlight novel signaling cues involved in the commitment program of multiciliated cells across species and tissues.