During embryonic development, a ‘protomap’ of the cortex forms in the developing brain region that will become the cerebral cortex. Robert Hevner and his colleagues at Seattle Children’s Research Institute are studying the mechanisms that maintain this patterning of regional identity throughout embryonic development.
They found that precursor cells to the radial glia in the ventricular zone (VZ), intermediate progenitors in the subventricular zone (SVZ), and projection neurons in the cortical plate (CP) each contain distinct molecular maps of regional identity.
These maps reflect different gene expression gradients in the different cells. Hevner’s team also determined that the ‘intermediate map’ in the SVZ is modulated by a T-box transcription factor called EOMES (also known as TBR2). EOMES, and the related T-box transcription factor TBR1, are key regulators of gene expression. When mutated in humans, they contribute to autism and cortical malformations.
Inactivation of EOMES causes shifts in the patterning of SVZ and CP gene expression, leading to loss of neuronal connections between the cortex and spinal cord, and gain of connections between the cortex and tectum, a region of the brain that is responsible for visual and auditory reflexes. These findings suggest that cortical areas and connections are shaped by sequential maps of regional identity that are defined by the genes PAX6, EOMES and TBR1. All three genes have been linked to intellectual disability and autism.