Medaka oct4 is essential for gastrulation, central nervous system development and angiogenesis

Abstract

Gene oct4 (also called oct3/4 or pou5f1) encodes an octamer-binding transcription factor and is best known for its pluripotency-specific expression and pluripotency-maintaining role in early embryos and embryonic stem cells of mouse and human. Its fish paralog oct4 (also called pou2 or pou5f3) plays divergent roles in embryos and stem cells development. Here the expression and function of the medaka oct4 (Oloct4) during gastrulation and organogenesis were analysed. Oloct4 RNA was abundant in pluripotent cells and differentiated extraembryonic cells of blastula embryos. It was also detectable in primordial germ cells, brain, eye and tail bud at advanced stages. Importantly, oct4 depletion at high dosages severely affected gastrulation and axis formation. Surprisingly, Oloct4 depletion at low dosages also led to embryos that either had defective brain, eye and/or blood vessels or completely lacked them. Oloct4 depletion in transgenic embryos caused the loss of rx2-positive retinal stem cells in the developing eye. Therefore, Oloct4 is essential for gastrulation, central nervous system development as well as angiogenesis in medaka besides its role in pluripotency maintenance. These results together with previous studies suggest that Oloct4 play pleiotropic roles and represent the ancestral prototype of vertebrate oct4 and pou2 genes.