Gene networks controlling early cerebral cortex arealization

Early thalamus-independent steps in the process of cortical arealization take place on the basis of information intrinsic to the cortical primordium, as proposed by Rakic in his classical protomap hypothesis [Rakic, P. (1988) Science, 241, 170–176]. These steps depend on a dense network of molecular interactions, involving genes encoding for diffusible ligands which are released around the borders of the cortical field, and transcription factor genes which are expressed in graded ways throughout this field. In recent years, several labs worldwide have put considerable effort into identifying members of this network and disentangling its topology. In this respect, a considerable amount of knowledge has accumulated and a first, provisional description of the network can be delineated. The aim of this review is to provide an organic synthesis of our current knowledge of molecular genetics of early cortical arealization, i.e. to summarise the mechanisms by which secreted ligands and graded transcription factor genes elaborate positional information and trigger the activation of distinctive area-specific morphogenetic programs.