Abstract
The brain of modern humans has evolved remarkable computational abilities that enable higher cognitive functions. These capacities are tightly linked to an increase in the size and connectivity of the cerebral cortex, which is thought to have resulted from evolutionary changes in the mechanisms of cortical development. Convergent progress in evolutionary genomics, developmental biology and neuroscience has recently enabled the identification of genomic changes that act as human-specific modifiers of cortical development. These modifiers influence most aspects of corticogenesis, from the timing and complexity of cortical neurogenesis to synaptogenesis and the assembly of cortical circuits. Mutations of human-specific genetic modifiers of corticogenesis have started to be linked to neurodevelopmental disorders, providing evidence for their physiological relevance and suggesting potential relationships between the evolution of the human brain and its sensitivity to specific diseases.
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Acknowledgements
The authors apologize to the many authors whose work could not be discussed owing to space constraints. They thank E. Schmidt for his help generating elements of Fig. 4. Work from the P.V. laboratory described here was funded by the European Research Council (ERC Advanced Grants GENDEVOCORTEX and NEUROTEMPO), the Belgian FWO and FRS/FNRS, the EOS Program, the AXA Research Fund, the Belgian Queen Elizabeth Medical Foundation, the ERA-NET NEURON and the Generet Fund. Work from the F.P. laboratory described here was funded by grants from NINDS (NIH grants RO1NS067557 and R35NS127232), an award from the Roger de Spoelberch Fondation and an award from the Nomis Foundation.
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Glossary
- Association areas
-
A class of cortical areas defined by their opposition to primary areas (cortical regions receiving direct inputs from the dorsal thalamus). Association areas are where different sensory and/or motor modalities combine and where complex cognitive processes such as attention, planning and memories are encoded.
- Cell fate mapping
-
A range of techniques aimed at genetically labelling the progeny of individual classes of progenitors, thereby reconstructing the lineage linking dividing progenitors and all the cells they generate.
- Chromatin loops
-
The situation in which stretches of genomic sequence that lie on the same chromosome (configured in cis) are in closer physical proximity to each other than they are to intervening sequences.
- cis-regulatory elements
-
Portions of genes containing the promoter and other regulatory elements controlling levels of gene transcription.
- Comparative genomics
-
A subfield of biology involving the analysis of DNA sequence divergence and conservation between different organisms.
- Connectome
-
A description of all the synaptic connections between neurons found within a brain region or the entire nervous system of an organism.
- Cortical organoids
-
Self-organized 3D multicellular structures that can be patterned to mimic the neocortex.
- Dendritic processing
-
The receipt, integration and processing of many synaptic inputs by dendrites. This processing takes the form of changes in membrane potential, which can — depending on the density and distribution of passive or active ionotropic channels — differentially affect the generation of action potentials at the level of the soma.
- Dendritic spines
-
Micron-long protrusions present in specific neuronal subtypes, such as cortical pyramidal neurons, at the tip of which is located an excitatory synapse. Spines play important roles in electrically and biochemically isolating the postsynaptic compartment from the dendrite shaft. Experimentally, morphologically identified dendritic spines represent a close approximation to measuring number or density of excitatory synapses received by a neuron.
- Epigenetic profiling
-
Molecular biology technique combined with biochemistry to monitor the post-translational modifications and physical interaction of DNA and chromatin and how they impact gene expression in cells.
- Heterochrony
-
Changes in the relative timing of a developmental event when different species or brain regions are being compared.
- Large segmental genomic duplications
-
Large segments (more than 1 kb) of the genome that have been duplicated in another position in the genome.
- Long non-coding RNAs
-
RNAs longer than 200 bp that are not translated into protein.
- Massively parallel reporter assays
-
A molecular biology technique used to simultaneously test the activity of multiple candidate genetic regulatory elements in a high-throughput manner.
- Morphogen
-
One of a class of extracellular cues that can act at a distance from its source and regulate gene expression in receiving cells and tissues and thereby play a central role in cell type specification or tissue patterning.
- Neurogenesis
-
The generation of postmitotic neurons by specialized classes of dividing progenitors.
- Single-cell RNA sequencing
-
A high-throughput sequencing technique used to determine the sequences of mRNA expressed in single cells, also referred to as the transcriptional profile of single cells.
- Topology-associated domains
-
Large self-interacting genomic regions (~1 Mb) physically interacting inside the nucleus. This level of chromatin organization plays key roles in regulating temporal and spatial patterns of gene expression in gene families such as the HOX cluster.
- Xenotransplantation
-
Transplantation of cells from one species into a different species.
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Vanderhaeghen, P., Polleux, F. Developmental mechanisms underlying the evolution of human cortical circuits. Nat Rev Neurosci 24, 213–232 (2023). https://doi.org/10.1038/s41583-023-00675-z
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DOI: https://doi.org/10.1038/s41583-023-00675-z
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