Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons.

Projection neurons destined for the cortical plate are generated sequentially from the proliferative ventricular and subventricular zones (VZ/SVZ) of the pallium. However, the respective contribution of both proliferative zones to the generation of cortical plate neurons is better established in humans and non-human primates than in rodents. We identified Cux2 as a new marker for murine cortical subpopulations and used it to provide new insights to the development of the mouse cortex. Cux2 is an orthologue of the Drosophila cut gene, which encodes a homeodomain protein involved in neuronal specification. During cortical development Cux2 identifies two subpopulations with different spatial origins, migratory behaviours and phenotypic characteristics: (i) a population of interneurons, which invades the pallium from the subpallium; and (ii) a neuronal population produced in the pallium around embryonic day 11.5, which divides in the SVZ and accumulates in the intermediate zone (IZ). Subsequently, Cux2 is a marker of upper cortical layers. Using different molecular markers and Pax6-deficient mice, we provide data that suggest a relationship between the early-determined Cux2-positive neuronal precursors in the SVZ/IZ and upper layer neurons. This suggests that laminar determination of upper cortical layer neurons occurs during the earliest stages of corticogenesis.