Whether or not similar mechanisms control cortical regionalization in humans has been ERK inhibitor difficult to establish, because manipulating transcription factor expression in highly controlled genetic backgrounds is not feasible. In this issue of Neuron, Chen and colleagues ( Chen et al., 2011) take on this challenge by using a potent combination of analytical strategies, a twin-study design and structural MRI, to address whether latent genetic factors contribute to regionalization of the cerebral cortex in humans. Specifically, by obtaining and analyzing MRI data from over 200 monozygotic and dizygotic twin pairs (from

the Vietnam Era Twin Study of Aging) ( Kremen et al., 2006), the authors derived cortical surface reconstructions using a spherical atlas mapping procedure to measure the relative contributions of genetic and environmental influences on the regional expansion of cortical surface area. In this way, they could generate a map that reveals a regional pattern of shared genetic influence on cortical surface area. Interestingly, they demonstrate that along the anterior-posterior axis, there is evidence for both positive and negative

genetic correlation effects on surface area. When related to a seed region in the frontal Tyrosine Kinase Inhibitor Library pole, positive correlations are seen to be strongest nearest the seed and to then taper off posteriorly to the central sulcus, where there is an abrupt transition to negative correlations that are still more posterior. The “push-me/pull-you” Bcl-w nature of these

relationships is highly reminiscent of the antagonistic relationship seen along the cortical anterior-posterior axis between transcription factors PAX6 and EMX2 in mouse studies (O’Leary et al., 2007). The authors also nicely demonstrate that the locations of transitions in shared genetic influence were comparable when derived via a seed-based approach or via a data-driven approach. These findings convincingly illustrate a pattern of genetic correlation for cortical surface area that reflects the aggregate effect of myriad genetic/intrinsic mechanisms. However, these results should not be construed as a cytoarchitectonic map of neocortical arealization or as a map that reveals the expression pattern of putative human homologs of the transcription factors described in the mouse literature. First, the granularity of the regionalization is at a scale larger than one would consider to be associated with neocortical areas. Rather, the regionalization appears to be of a lobar (such as frontal or parietal) or sublobar, not areal, scale. For example, the data reveal no evidence of a delineation between V1 (primary visual cortex) and V2 on the medial surface.