Non-cell autonomous Otx2 homeoprotein regulates visual cortex plasticity through Gadd45b

The non-cell autonomous transfer of Otx2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2+/GFP mice at plastic and non-plastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. We find that Otx2 transfer regulates Gadd45b/g expression, which can potentially modify the epigenetic state of parvalbumin interneurons as evidenced by changes in MeCP2 foci size and number. Blocking Otx2 transfer in the adult, which induces plasticity, resulted in Gadd45b/g upregulation and changes in MeCP2 foci. Viral expression of Gadd45b in adult visual cortex directly induced plasticity with concomitant changes in MeCP2 foci. This interaction provides a molecular mechanism for Otx2 to promote critical period plasticity yet suppress adult plasticity.