Genes Responsible for Maintaining Embryonic Developmental Potential

A major question concerning early embryos involves how early cleavage-stage (two-cell) embryos establish unlimited developmental potential - termed totipotency. Cairns and colleagues identified the multicopy retrogene, DUX4 in humans or Dux in mice, as a transcription factor that is turned on in very early embryos and activates hundreds of genes and retroviral elements during cleavage stage. Remarkably, the expression of Dux efficiently converts mouse embryonic stem cells into 2-cell-embryo-like cells (2CLC) with expanded developmental potential. Interestingly, these 2CLC can contribute to either embryonic or extra-embryonic (trophectoderm/placenta) cell lineages. Thus, Dux-family proteins appear to play essential roles in determining developmental potential in early embryos. The improper expression of DUX4 underlies the common muscle disease facioscapulohumeral muscular dystrophy (FSHD), and the results from this work provide important and novel information on the typical role of DUX4 that can now be explored in the context of FSHD.