Fig. 7. Model of the three steps involved in PPE formation. (1) The embryonic ectoderm is separated into presumptive epidermis (E), pre-placodal (P), neural crest (NC) and neural plate (NP) domains in response to a combination of a dorsoventral gradient of BMP-antagonizing factors (Noggin) and a gradient of posteriorizing signals (Wnt, FGF). (2) six1 promotes the expression of placode genes at the expense of neural crest and epidermal genes. (3) A network of gene interactions further defines the ectodermal subdomains. Green arrows indicate that the expression of the downstream gene is enhanced, and red bars indicate that it is reduced. Lines are broken to indicate that interactions may be direct or include intermediary genes.