A natural transdifferentiation event involving mitosis is empowered by integrating signaling inputs with conserved plasticity factors
Abstract
Transdifferentiation, or direct cell reprogramming, is the conversion of one fully differentiated cell type into another. Whether core mechanisms are shared between natural transdifferentiation events when occurring with or without cell division is unclear.
We have previously characterized the Y-to-PDA natural transdifferen-tiation in Caenorhabditis elegans, which occurs without cell division and requires orthologs of vertebrate re-programming factors. Here, we identify a rectal-to-GABAergic transdifferentiation and show that cell division is required but not sufficient for conversion.
We find shared mechanisms, including erasure of the initial iden-tity, which requires the conserved reprogramming factors SEM-4/SALL, SOX-2, CEH-6/OCT, and EGL-5/ HOX. We also find three additional and parallel roles of the Wnt signaling pathway: selection of a specific daughter, removal of the initial identity, and imposition of the precise final subtype identity.
Our results sup-port a model in which levels and antagonistic activities of SOX-2 and Wnt signaling provide a timer for the acquisition of final identity.