A changing signaling environment induces multiciliated cell trans-differentiation during developmental remodeling

Abstract

Multiciliated cells (MCCs) are extremely highly-differentiated, presenting >100 cilia and basal bodies. We analyzed how MCCs are lost from the airway-like Xenopus embryonic epidermis during developmental tissue remodeling. We found that some MCCs undergo apoptosis, but that the majority trans-differentiate into secretory cells. Trans-differentiation involves loss of ciliary gene expression, cilia retraction and lysosomal degradation. Apoptosis and trans-differentiation are both induced by a changing signaling environment through Notch, Jak/STAT, Thyroid hormone and mTOR signaling, and trans-differentiation can be inhibited by Rapamycin. This demonstrates that even cells with extreme differentiation features can undergo direct fate conversion. Our data further suggest that the reactivation of this developmental mechanism in adults can drive tissue remodeling in human chronic airway disease, a paradigm resembling cancer formation and progression.

Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells

“…After incubation in 100% HMDS, the solvent was allowed to evaporate. The dehydrated tissue was mounted onto sample holders and sputtered with gold using Polaron Cool Sputter Coater E 5100 ( 92 ). Quantification of foot process effacement was done by counting slit diaphragms in TEM micrographs and setting the resulting numbers in relation to the length of the basement membrane, resulting in a SD/μm.…”