Expression of the genes encoding Reelin and Dab1 during cortical development in turtle, lizard, chick and mammals correlates with architectonic patterns. In all species, Reelin is secreted by marginal zone cells, whereas Dab1, which mediates the response to Reelin, is synthesized by cortical plate neurons. This pattern was presumably present in stem amniotes. In mammals, the cortical plate is radially organized and develops from inside to outside, these features depend on amplification of reelin synthesis in the marginal zone. In lizards, the cortical plate develops from outside to inside, similar to other non-mammals, but is radially organized, with an additional layer of Reelin added in the subcortex. Thus, the Reelin pathway played a key role in cortical architectonic evolution in mammalian and squamate lineages.