Jaclyn Rebertus

The mammalian neocortex possesses a complex cytoarchitecture that is necessary for maintaining proper neurological function. Aberrant laminar organization of the cortex has been implicated in a variety of disorders, including autism and epilepsy. Prior work has shown that this architecture is, in part, influenced by input from neuronal connections originating in the thalamus and may involve VGF, a neuropeptide precursor that is secreted from thalamocortical axons. When these thalamocortical projections were abolished in our genetic mouse model, the distribution of neurons across the six layers of the cortex was disturbed. However, the mechanism by which thalamocortical axons exert their influence is unknown. To test the hypothesis that the thalamus-derived VGF controls the output of cortical neurogenesis, we utilized a thalamus-specific conditional knockout of Vgf and analyzed neuron numbers in each layer and the fate of neural progenitor cells that become postmitotic at a certain embryonic stage. We found that Vgf knockout mice displayed an alteration in the number of superficial layer neurons in primary somatosensory and visual areas. Specifically, the number of neurons in layer 4 was significantly less in the knockout mice, and the number of layer 2/3 neurons was unchanged or increased when compared to controls. Additionally, the proportion of postmitotic neurons in layer 4 to layer 2/3 was significantly decreased in Vgf knockouts. These results suggest that VGF plays a role in modulating the switch in laminar fate, and its absence may result in a premature shift from layer 4 to layer 2/3 neurogenesis.