Development of the Pre-Placodal Ectoderm and Cranial Sensory Placodes

Cranial sensory placodes arise from a common precursor field, the pre-placodal ectoderm (PPE), which surrounds the anterior neural plate just lateral to the neural crest. They give rise to secretory cells and numerous sensory structures in the vertebrate head. The PPE forms in response to interactions between the neural and non-neural ectoderm and to signaling factors (FGF, BMP, Wnt and retinoic acid) from adjacent tissues (underlying mesoderm, endoderm, anterior neural ridge). Members of the Six family of transcription factors, particularly Six1 and Six4, are major regulators of PPE fate specification. Six1 upregulates other placode genes and downregulates epidermal and neural crest genes, thus maintaining PPE/placodal fate. Several co-factor proteins, including members of the Eya, Groucho and Dachund families, modify Six protein activity. The PPE is initially competent to form all of the different placodes. Signaling from adjacent tissues along its anterior-posterior extent activates different sets of transcription factors that cause the PPE to separate into individual placodes with different developmental fates. Six1 and Eya1 maintain placode cells in an undifferentiated, proliferative state. They are downregulated when differentiation is initiated. For placode-derived neurons, this involves a dose-dependent regulation of SoxB1 transcription factors. Mutations in SIX and EYA genes underlie several human syndromes whose phenotypes often include hearing loss.