Cell interactions, signals and transcriptional hierarchy governing placode progenitor induction [RESEARCH ARTICLE]

Mark Hintze, Ravindra Singh Prajapati, Monica Tambalo, Nicolas A. D. Christophorou, Maryam Anwar, Timothy Grocott, and Andrea Streit

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.

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