Contribution of mechanical forces in multiciliated cell differentiation

Multiciliated cells, through the coordinated beating of motile cilia, are vital for moving fluids in the brain and mucus in the airways and in the reproductive organs. Their dysfunction leads to diseases, associated with chronic airway infections, subfertility and ventricular enlargement. A group of transcription factors and a cell cycle variant enable the differentiation of multiciliated cells. However, how the multiciliated differentiation programme is initiated, timed and spatially regulated within developing tissues remains unclear. In this review, we combine findings from airway, brain ventricles and Xenopus epidermal systems to reveal how mechanical cues may interact with transcriptional networks and cell cycle regulators during multiciliogenesis. We suggest a model where mechanical forces serve as contextual regulators that enable, time and control the execution of the multiciliated differentiation programme.