Repressive roles of Erf and Elk in FGF-regulated neural development in Ciona intestinalis

Abstract The emergence of new cell types, such as the neural crest and placodes in vertebrates, often relies on conserved signalling pathways that are newly interpreted at the transcriptional level. The dynamic network of multiple ETS transcriptional effectors downstream of RTK/ERK signalling is poorly understood despite its central role in development and cancer. We examined how co-existing ETS repressors and ETS activators interpret FGF/ERK signalling at successive binary cell fate choices in the invariant neural developmental lineage of tunicates/ascidians. Genetic interference shows that both Erf and Elk act as repressors, playing successive roles at different transcriptional targets. We propose an ETS site occupancy model in which ETS activators and repressors compete for the same DNA binding sites, and whereby the different balance of this competition drives adjacent cells towards opposing fates. This mechanism provides a general framework for ERK/ETS factor-controlled cell fate switching in adjacent territories, also beyond ascidians. It may further the interpretation of other ETS activator and repressor activities including Elk-mediated repression in neural crest specification and deregulation downstream of ERK in stem cells and cancer.