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Legend: Lack of tangential migration of glutamatergic (left) but not GABAergic (right) neurons during chick brain development. The left diagram demonstrates that no tangentially migrating glutamatergic neurons leave from the labelled segment of the neuroepithelium (cortical haem) in the embryonic chick brain, which normally produce such neurons in mammals. The right panels demonstrate that GABAergic interneurons (green) are the only population that arrives tangentially to the dorsal area of the forebrain (red) from external sources. Interneurons were labeled at their site of origin in the subpallium with a plasmid DNA encoding the green fluorescente protein. The dorsal area of the forebrain is labelled in red by immunohistochemistry against the transcription factor Satb2.

Origins of the mammalian cerebral cortex is linked to changes in the migration of the earliest born neuronal populations.

The cerebral cortex makes us human. It is responsible for our higher cognitive functions, such as language, retaining our memory of the past, planning for the future, and appreciating or producing science and art.  Although all mammals have this characteristic, a laminated cerebral cortex is only found in primates and humans where the cerebral cortex reaches its maximum complexity.

Reptiles and birds have no laminated cerebral cortex.  They are able to accomplish their sensory, motor and cognitive functions because their brains enlarge a different sector of the neuroepithelium, from which the cerebral cortex develops, than the one that produces the cerebral cortex in mammals. In avian and reptilian brains a large ball of neurons is generated from a region that is adjacent to the sector that generates cerebral cortex in mammals. This ball of neurons is comprised of nuclei, rather than layers.

One of the most fundamental questions in evolutionary biology is how mammalian cerebral cortex, the most complex organ of nature, appeared during evolution, between 300 and 170 million years ago, and to understand what triggered the changes in the development in the common ancestor that started to produce a laminated dorsal cortex in mammals and started to generate the large ball of neurons with nuclei in birds.

A study by Fernando García-Moreno and colleagues, published in the journal Cell Reports, investigated the early embryonic development of the chicken brain and compares this with mammals.  The study found some fundamental differences in the earliest generated neurons between mammalian and avian brains that may have triggered the divergent evolution. 

The development of the laminated mammalian cerebral cortex is orchestrated with early born transient neuronal populations originating from sites outside the cerebral cortex.  These neurons arrive to the cortex through migration before the generation cortical neurons. They promote the generation of cortical layers, orchestrate the formation of the appropriate connection between brain regions or promote the production of the appropriate number of cortical neurons.  After completion of development most of these neurons die and disappear from the cortex.   

Until now it was not known if migratory neurons exist only in mammals, the only animals with neocortex, the part of the brain involved in high-order functions such as language, or if on the contrary they migrate and behave in the same way in other species.  The international research team led by García Moreno, from Bilbao, and Professor Zoltán Molnár, from DPAG, traced the cellular movements of three brain regions that are equivalent to the ones that give rise to early-generated transient neurons in mammals.  

Surprisingly, the study found that although all the three regions produced neurons in the chick, they stayed at the site of their genesis and in no case did they migrate in the same pattern towards the putative location of the cortex observed in mammals.  

Given their relevance in the development of the brain and their transitory nature, these migratory cells could have been decisive in the evolutionary origin of the mammalian neocortex, and their appearance could have that which made possible the appearance of the neocortex.  The study also compared relevant gene expression patterns between mammalian and avian brains and speculated about what lead to these fundamental changes. 

Understanding the cellular and molecular mechanisms that evolved to generate mammalian brain is fundamental not only to understanding our own origins, but also to understanding the various developmental conditions that can affect cortical functions.

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