The transcription factor Oct4 / Pou5f1 is a major regulator of pluripotency in embryonic stem cells. However, its functions in the early embryo and the evolution of the pluripotency regulatory network are not well understood. We investigate the regulation of developmental control genes and pluripotency network components in the early zebrafish embryo. Our data have shown a fundamental involvement in temporal control of the early embryonic transcriptional networks (Onichtchouck et al. MSB 2010), and an evolutionary origin of the Oct4 / Pou5f1 regulatory network in zygotic genome activation (Leichsenring et al., SCIENCE 2013). We further use the gastrulation and cell behavior defects in Oct4 / Pou5f1 mutant embryo as experimental system to study control of cell behavior, adhesion and migration, during gastrulation (Song et al., DEV. CELL 2013).

 

A biomedically relevant cell differentiation paradigm is the differentiation of dopaminergic neurons, which are affected in Parkinson's and other neurological diseases. We investigate the signaling and transcriptional networks that control specification and differentiation of different dopaminergic neuron groups in the zebrafish embryo and larvae (Filippi et al., DEV. BIOL. 2012). Using systems biology and virtualization tools, we aim to understand the complex networks of dopaminergic neuron differentiation (Ronneberger et al. NATURE METH 2012). Our interest extends into mechanisms to generate functional axonal connections of dopaminergic neurons to their targets (Tay et al. NATURE COM. 2011; Schweitzer et al., DEVELOPMENT 2013). Zebrafish will be an excellent model to link development and function of dopaminergic neuromodulation to control behavior (Arrenberg and Driever, FRONT. NEUROSCI. 2013).