Genetic and developmental homology in amniote brains. Toward conciliating radical views of brain evolution.

The six-layered neocortex is both a unique and a universal character of mammals. Historically, a major concern has been to determine its phylogenetic origins by establishing which structures, if any, correspond to it in the brains of other vertebrates. Two opposing hypotheses have been debated in the last years: (i) the neocortex arises entirely from the dorsal hemisphere of ancestral reptiles, and (ii) a large portion of it originates in the lateral hemisphere, from a structure termed the dorsal ventricular ridge (DVR), which expands significantly in reptiles and especially in birds. While developmental and genetic evidence strongly favors a dorsal origin of the neocortex, there are important similarities in the sensory connectivity to the neocortex and to the DVR, and more recently, in the phenotype of late-produced elements in both structures. It is proposed that, despite originating in different embryonic domains, the proliferative expansion of both the mammalian neocortex and the sauropsidian DVR is partly based on the amplification of similar developmental programs, possibly dependent on Pax6 activity or of related cascades that promote progenitor proliferation. While Pax6 activity is already present in the amphibian pallium, I propose that at some point(s) in amniote evolution it has been upregulated yielding brain expansion in both sauropsids and mammals. However, in the latter there has been an additional dorsalizing influence contributing to the development of the neocortex and restricting the expansion of the lateral hemisphere. Finally, a significant contribution to neocortical origins by anterior signaling centers secreting FGFs is suggested, by virtue of their association to olfactory development and their cortical patterning functions. This perspective fits a dynamical view of brain homology, where instead of searching for a one-to-one correspondence between components, emphasis is placed on changes in the modulation of conserved signaling centers and their corresponding morphogen gradients across species.