The Molecular Regulation of Cranial Placode Specification

In vertebrate embryos, interactions between the neural and the non-neural ectoderm induce a border zone surrounding the neural plate that contains the precursors of the neural crest and the pre-placodal ectoderm (PPE). The PPE then breaks up into individual placodes that give rise to several cranial sensory structures including the olfactory epithelium, lens, cranial ganglia, inner ear and lateral line. Although the PPE and neural crest arise from a common zone, these two precursor populations are differentially affected by Wnt signaling and they express distinctly different sets of transcription factors. In particular, members of the Six transcription factors family and of the Eya co-factor family are required for PPE formation and placode differentiation. We are characterizing the gene interactions that set up the boundaries between the PPE and adjacent embryonic ectodermal domains. We find that genes required for neural crest specification also repress Six1 expression. Conversely, Six1 represses neural crest specifier genes. Likewise, Six1 represses epidermal transcription factors, and vice versa. These results indicate that mutual repression establishes fate boundaries between neural crest, PPE and epidermis during patterning of the embryonic ectoderm.