333 Ciliophagy governs transdifferentiation of multiciliated cells in Xenopus embryonic skin

Abstract

Cilia are microtubule-based structures that protrude from the cell surface. Primary cilia function as sensors for environmental signals to regulate cell fate decisions and motile cilia produce directed fluid flow. In multiciliated cells (MCCs) there is a dynamic and intricate process that allows for the generation of greater than 150 evenly-spaced cilia, which coordinate to produce directed fluid flow over the epithelial surface. Induction of this MCC fate is restricted by Notch signaling, whereas activation of Notch signaling promotes secretory cell formation. It has been proposed that MCCs have the potential to resorb their cilia and transdifferentiate into secretory cells, however the mechanisms coordinating this transdifferentiation processes remain unknown. In order to address this, we utilized Xenopus embryonic skin as a model system. In Xenopus skin development, MCCs intercalate into to the outer epithelial layer that is composed of secretory cells. We have found that as Xenopus embryos continue to mature MCCs begin to lose their cilia-driven fluid flow as a result of cilia resorption followed by transdifferentiation into secretory cells. At this time, MCCs generate large intracellular vacuoles and the autophagosome protein LC3 localizes to the base of cilia suggesting that autophagy of cilia components, ciliophagy, is an important process in transdifferentiation. Since MCCs are a fully differentiated cell, the potential to coordinate large-scale ciliophagy for transdifferentiation represents a surprising and remarkable process. Our results demonstrate that Xenopus skin can be used to better understand the mechanistic links between cilia resorption, autophagy, and Notch signaling during transdifferentiation of epithelial cells.