Hypothesis for the evolution of chordate Pax2/5/8 subfunctions. In stem chordates, Pax2/5/8 already played a role during the development of the endostyle, the homolog of the vertebrate thyroid, as well as in controlling genes for making epithelial fusions and perforations (for example, gill openings). The Pax2/5/8 subfunction related to the development of neurogenic placodes (for example, otic placode) appears to be restricted to the olfactores; like vertebrate orthologs, urochordate Pax2/5/8a genes are expressed from just after neurula stage in paired thickenings overlapping the early expression of other placode-marking genes . Inferred origins for some of the functions (circles in stems) performed by the pleiotropic Pax2/5/8 gene family and inferred subfunction partitioning are schematized in the context of the chordate phylogeny. Gene duplication events (stars) in different chordate lineages permitted independent partitioning of endostyle/thyroid (red circles) and otic placode (blue circles) subfunctions among gene paralogs. Half semicircles denote dorsal and ventral expression domains. Pale blue circles denote paralogs whose expression is inferred to have become delayed, transient or spatially narrowed in development of the otic system. White circles indicate inferred subfunction losses. [43, 45, 48, 52, 56, 73, 84, 85, 118, 119].