Cell interactions, signals and transcriptional hierarchy governing placode progenitor induction

In vertebrates, cranial placodes contribute to all sense organs and sensory ganglia and arsise from a common pool of Six1/Eya2+ progenitors. Here we dissect the events that specify ectodermal cells as placode progenitors using newly identified genes upstream of the Six/Eya complex. We show that two different tissues, the lateral head mesoderm and the prechordal mesendoderm, gradually induce placode progenitors: cells pass through successive transcriptional states, each identified by distinct factors and controlled by different signals. Both tissues initiate a common transcriptional state, but over time impart regional character and the acquisition of anterior identity depends on Shh signalling. Using a network inference approach we predict the regulatory relationships among newly identified transcription factors and verify predicted links using knock-down experiments. Based on this analysis we propose a new model for placode progenitor induction, in which the initial induction of a generic transcriptional state precedes regional divergence.