In spite of its stereotypic laminar and columnar organization, the cerebral neocortex displays numerous species-specific adaptations of old and acquired new traits that subserve specific functions introduced during 100 million years of mammalian evolution.
The human neocortex, a substrate of our unique cognitive abilities, has many distinct traits in addition to a larger surface, including different places of neuronal origin, distinct migratory pathways and acquisition of new cell types that were traditionally studied by comparative anatomists.
The contemporary, evo–devo approach uses developmental principles and mechanisms uncovered by experiments in embryos of living species to obtain a glimpse into how the human neocortex may have developed at the cellular and molecular level in extinct common ancestors.
The radial unit model of cortical evolution provides insight into how mutation of genes that control the transition from the symmetric to asymmetric mode of cell division in the proliferative ventricular zone subjected to radial constraint during migration can generate neocortical expansion in surface rather than in thickness.
The protomap hypothesis of differential enlargement of the existing and introduction of new cytoarchitectonic areas has been tested in mouse embryos by mutation and/or changes of gene expression and transcriptional factors in the neural stem cells of the proliferative ventricular and subventricular zones.
Understanding of the species-specific difference in tempo and sequence of cortical development as well as genesis of new cell subtypes, functional columns and synaptic connectivity is essential for design of therapies for trauma, congenital malformations, neurodegenerative disorders and ageing of the human cerebral neocortex.
The enlargement and species-specific elaboration of the cerebral neocortex during evolution holds the secret to the mental abilities of humans; however, the genetic origin and cellular mechanisms that generated the distinct evolutionary advancements are not well understood. This article describes how novelties that make us human may have been introduced during evolution, based on findings in the embryonic cerebral cortex in different mammalian species. The data on the differences in gene expression, new molecular pathways and novel cellular interactions that have led to these evolutionary advances may also provide insight into the pathogenesis and therapies for human-specific neuropsychiatric disorders.
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I am grateful to the former and present members of my laboratory whose skills, wisdom, hard work and insightful discussions made this article possible. I am also grateful to the U.S. Public Health Service and private philanthropic organizations that provided funding over the past four decades including NINDS, NEI, NIMH, NIDA, March of Dimes, NARSAD, NAAR and MOD Foundations and the Kavli Institute for Neuroscience at Yale.
The author declares no competing financial interests.
- Transient embryonic layers
Layers identified in the embryonic brain, such as the proliferative ventricular and subventricular zones (VZ/SVZ) or migratory intermediate zone that lack direct counterparts in the adult brain, as defined by the Boulder Committee.
The tissue situated between neuronal cell bodies, composed of a complex network of neuronal and glial processes including dendrites, dendritic spines, axonal terminals and synapses, used often to measure connectedness of a given structure.
- Cortical parcellation
Regionalization of the cerebral neocortex into areas with distinct structural and functional attributes.
- Patterning center
Group of cells in the embryonic brain that secrete molecules (morphogens) that initiate differential expression of transcription factors that specify formation of the cortical areas.
- Homotypic–neurophilic guidance
Mode of neuronal migration along the surface of other neurons that depends on membrane-bound adhesion molecules present on both migrating and guiding neurons as opposed to heterotypic gliophilic migration that is guided by the shafts of radial glial cells.
- Association areas
Areas of the neocortex that are particularly large in the human cortex (for example, prefrontal granular cortex or language-related Broca and Wernicke areas) are considered as analysers for integration of information from various sensory and motor areas.
- Network of genes
A collection of genes that are co-regulated or interact with each other.
A short region of DNA to which proteins including transcription factors can bind to enhance transcription levels of genes in gene clusters.
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Rakic, P. Evolution of the neocortex: a perspective from developmental biology. Nat Rev Neurosci 10, 724–735 (2009). https://doi.org/10.1038/nrn2719
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