Abstract
Essentially we show recent data to shed new light on the thorny controversy of how teeth arose in evolution. Essentially we show (a) how teeth can form equally from any epithelium, be it endoderm, ectoderm or a combination of the two and (b) that the gene expression programs of oral versus pharyngeal teeth are remarkably similar. Classic theories suggest that (i) skin denticles evolved first and odontode-inductive surface ectoderm merged inside the oral cavity to form teeth (the 'outside-in' hypothesis) or that (ii) patterned odontodes evolved first from endoderm deep inside the pharyngeal cavity (the 'inside-out' hypothesis). We propose a new perspective that views odontodes as structures sharing a deep molecular homology, united by sets of co-expressed genes defining a competent thickened epithelium and a collaborative neural crest-derived ectomesenchyme. Simply put, odontodes develop 'inside and out', wherever and whenever these co-expressed gene sets signal to one another. Our perspective complements the classic theories and highlights an agenda for specific experimental manipulations in model and non-model organisms.