Jaclyn Rebertus

The mammalian neocortex is composed of millions of neural cells called neurons. Neurons acquire specific physiological characteristics and organize into six layers throughout development. The organization of neurons within and across these neocortical layers underlies the function and formation of different cortical areas. The formation of these areas involves cues intrinsic to the cortex, such as transcription factor gradients, and extrinsic cues from the thalamus. Both of these systems have temporal and spatial specificity and interact reciprocally to achieve cortical organization. However, whether the interaction between the intrinsic and extrinsic mechanisms is also time-dependent is unknown. In order to test how cortex-intrinsic cues interact with the influence of the thalamus, we analyzed mutant mice in which Mettl14, a protein required for adenosine methylation of mRNAs, was specifically deleted in early embryonic cortex. We found that when Mettl14 was knocked out in the early embryonic cortex, thalamocortical axonal projections to the cortex were aberrant, and the formation of the cortical plate was delayed. Further, Mettl14 knockouts displayed abnormal distributions of neural progenitor cells at these stages. In early postnatal development, there was a loss of layer-4 specific neuron markers. Overall, our results demonstrate that Mettl14 has many roles in thalamocortical development at different stages.