Activin/Nodal signaling supports retinal progenitor specification in a narrow time window during pluripotent stem cell differentiation to anterior neuroectoderm. Mus musculus

In this study, we used chemically-defined media to induce the in vitro differentiation of mouse embryonic stem cells (ESCs) towards eye field fates. Inhibition of Wnt/ß-Catenin signalling was sufficient to drive ESCs to telencephalic, but not retinal fates. Instead, retinal progenitors could be generated from competent differentiating mouse and human ESCs by the activation of Activin/Nodal signaling within a narrow temporal window corresponding to the emergence of primitive anterior neural progenitors. Our results reveal insights into the mechanisms of eye field specification and open new avenues towards the generation of retinal progenitors for translational medicine. Overall design: Gene expression was evaluated in sorted RAX::GFP-positive and -negative ES cells at 10 days of in vitro differentiation upon treatment with Wnt inhibitor and Activin A or Sonic Hedgehog Agonist; global profiles were compared to E12.5 mouse embryo cortex, hypothalamus/diencephalon and eye.