Decision letter: Genetic mechanisms control the linear scaling between related cortical primary and higher order sensory areas

Abstract

The neocortex is the most recently evolved part of the human brain. It is associated with higher thought processes, including language and the processing of information from our senses. Anatomically, the neocortex is organised into different regions called ‘primary areas’ and ‘higher order areas’, and perturbations to this organisation are associated with disorders such as autism. There are many more higher order areas than primary areas in a mammalian brain. But, while primary areas are known to be specified by developmental genes in the embryo, little is known about how the development of higher order areas is controlled. Recent findings suggested that primary areas might themselves influence the emergence of higher order areas via a series of developmental events. Now, Zembrzycki, Stocker et al. have investigated the developmental mechanisms that organise the mouse neocortex into its different regions. The experiments involved mouse mutants that produce either too much or too little of a protein called Emx2. This protein is known to determine the size and position of the primary visual area (commonly called V1) during embryonic development. In the mutant mice with too much Emx2, the primary visual area was about 150% larger than it should be, even though the neocortex was a normal size. Zembrzycki, Stocker et al. then went on to show that the higher order areas associated with the primary visual area also grew proportionally larger in these mutant mice. The opposite was true for mice that didn’t produce Emx2 in their brains, and these mice had a much smaller primary visual area than normal mice. Together, these findings reveal a previously unknown linear relationship between the size of the primary visual area and higher order visual areas that is controlled by the genes that pattern the neocortex during development. This and other new insights will inform future studies of the development and organization of the neocortex and our understanding of how it evolved.