Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development.

The transcription factor POU5f1/OCT4 controls pluripotency in mammalian ES cells, but little is known about its functions in the early embryo. We used time-resolved transcriptome analysis of zebrafish pou5f1 MZspg mutant embryos to identify genes regulated by Pou5f1. Comparison to mammalian systems defines evolutionary conserved Pou5f1 targets. Time-series data reveal many Pou5f1 targets with delayed or advanced onset of expression. We identify two Pou5f1-dependent mechanisms controlling developmental timing. First, several Pou5f1 targets are transcriptional repressors, mediating repression of differentiation genes in distinct embryonic compartments. We analyze her3 gene regulation as example for a repressor in the neural anlagen. Second, the dynamics of SoxB1 group gene expression and Pou5f1-dependent regulation of her3 and foxD3 uncovers differential requirements for SoxB1 activity to control temporal dynamics of activation, and spatial distribution of targets in the embryo. We establish a mathematical model of the early Pou5f1 and SoxB1 gene network to demonstrate regulatory characteristics important for developmental timing. The temporospatial structure of the zebrafish Pou5f1 target networks may explain aspects of the evolution of the mammalian stem cell networks.