Building a ciliated epithelium: Transcriptional regulation and radial intercalation of multiciliated cells.

The epidermis of the Xenopus embryo has emerged as a powerful tool for studying the development of a ciliated epithelium. Interspersed throughout the epithelium are multiciliated cells (MCCs) with 100+ motile cilia that beat in a coordinated manner to generate fluid flow over the surface of the cell. MCCs are essential for various developmental processes and, furthermore, ciliary dysfunction is associated with numerous pathologies. Therefore, understanding the cellular mechanisms involved in establishing a ciliated epithelium are of particular interest. MCCs originate in the inner epithelial layer of Xenopus skin, where Notch signaling plays a critical role in determining which progenitors will adopt a ciliated cell fate. Then, activation of various transcriptional regulators, such as GemC1 and MCIDAS, initiate the MCC transcriptional program, resulting in centriole amplification and the formation of motile cilia. Following specification and differentiation, MCCs undergo the process of radial intercalation, where cells apically migrate from the inner layer to the outer epithelial layer. This process involves the cooperation of various cytoskeletal networks, activation of various signaling molecules, and changes in cell-ECM and cell-cell adhesion. Coordination of these cellular processes is required for complete incorporation into the outer epithelial layer and generation of a functional ciliated epithelium. Here, we highlight recent advances made in understanding the transcriptional cascades required for MCC specification and differentiation and the coordination of cellular processes that facilitate radial intercalation. Proper regulation of these signaling pathways and processes are the foundation for developing a ciliated epithelium.