Table 1 Carroll's 11 principles and the pluripotency genes of the case study.

"Mosaic pleiotropy", "Heterotopy"

Role in early embryonic cells, germ cells.

Role in early embryonic cells, germ cells, neural development.

Role in early embryonic cells, somite organization.

"Ancestral genetic complexity", "Deep homology"

All three genes are involved in vertebrate development; cooperation of POU and Sox factors is implicated in bilaterian development (fruit fly and vertebrate).

"Functional equivalence of distant homologs"

Various 'rescue experiments' in mice, e.g. using Oct4 from chicken [85], frog & axolotl [86].

?

?

"Infrequent toolkit gene duplication"

At most one paralog (pou2/pouv in monotremes & marsupials; Pou5f2 in rodents & primates).

Two close paralogs not expressed in the early embryo (Sox1, Sox3; [87]); three more remote paralogs that may substitute in Oct4 binding (Sox4, Sox11, Sox15).

No known close paralogs.

"Modularity of cis-regulatory elements"

Different roles of the distal and the proximal element.

Different regulatory elements in early embryonic vs. neural tissues.

?

"Vast regulatory networks"

All three genes are part of the large regulatory network underlying pluripotency; see [24, 25, 88].