<EM >IN VIVO </EM>TRACKING OF NASCENT TRANSCRIPTION AND TRANSLATION REVEALS<EM> DISTINCT </EM>AND<EM> DISCONTINUOUS </EM>ACTIVITY IN THE DEVELOPING NEOCORTEX

The neocortex is an evolutionarily recent brain region in mammals. It is structured into layers with distinct circuits. Progenitors in the ventricular zone generate neurons, which migrate towards their ultimate layers in the cortical plate for differentiation. Gene expression programs are tightly regulated in space and time to generate these neuronal lineages. Gene expression profiling thus far has relied on snapshots of the transcriptome and proteome; however, the timing and location of gene transcription and translation is unknown. We have met this challenge with an innovation to track nascent transcription and translation in the developing neocortex in real-time in vivo. In doing so, we make several surprising discoveries regarding neocortex gene activity. This includes a mismatch between the timing and location of nascent transcription and translation, and a striking pause in transcription during neuronal migration, followed by reactivation in the cortical plate. Thus, we introduce a broadly applicable method to track gene activation, and advance new concepts of gene “expression” in neocortex neurodevelopment.