Transcriptional networks for pluripotency are largely considered in the context of mammalian development, but the extent to which these function in other deuterostomes is unclear. Now, Yoshiyuki Seki and colleagues investigate the evolutionary origin of pluripotency by studying the function of PRDM14 from zebrafish, amphioxus and sea urchin. In mice, PRDM14 is expressed in pluripotent cells and germ cells where it regulates DNA methylation of pluripotency sites with co-factors such as TET1/2 and CBFA2T2. Using PRDM14 knockout mouse embryonic stem cells, the authors reveal that PRDM14 from zebrafish and amphioxus can compensate for endogenous gene loss and support self-renewal. In addition, co-immunoprecipitation experiments demonstrate that PRDM14 from zebrafish and amphioxus can bind with mouse TET1/2 and CBFA2T2. Conversely, PRDM14 from sea urchin is able to interact with mouse TET1/2, but not CBFA2T2, and can only rescue pluripotency when co-expressed with sea urchin CBFA2T. These results suggest that the ability of PRDM14 to maintain pluripotency relies on complex formation with CBFA2T. Finally, the study shows that, unlike in mammals, PRDM14 and CBFA2T2 are expressed by developing motor neurons in amphioxus, which is similar to what has previously been found in zebrafish. Taken together, these data indicate a conserved evolutionary origin for PRDM14-CBFA2T interaction, which was co-opted from motor neurons during vertebrate evolution to regulate pluripotency in amniotes.
