Foxg1 promotes Grin1 translation in neocortical neurons

Mainly known as a transcription factor patterning the rostral brain and governing its histogenesis, Foxg1 has been also detected outside the nucleus, however biological meaning of that has been only partially clarified. Here, moving from widespread Foxg1 expression in axons and dendrites of neocortical glutamatergic neurons, we investigated its implication in translational control. We documented an impact of Foxg1 on ribosomal recruitment of Grin1-mRNA, encoding for the main subunit of NMDA receptor. Next, we showed that Foxg1 increases Grin1 protein level by enhancing translation of its mRNA, while not increasing its stability. Such enhancement was associated to increased translational initiation and, possibly, polypeptide elongation. Molecular mechanisms underlying that included Foxg1 interaction with Eif4e, Eef1d and Pum1 as well as with Grin1-mRNA. Besides, we found that Grin1 de novo synthesis becomes particularly prominent in silent neurons and Foxg1 is needed for that. Finally, a dedicated TRAP-seq survey showed that functional Foxg1 implication in translation is a pervasive phenomenon, affecting hundreds of synaptic genes. All that points to Foxg1 as a key effector, crucial to prompt tuning of neocortical pyramid activity, namely an issue with profound physiological and neuropathological implications.