Issue: Anthropology and disability
Author: Vlaams Instituut voor Biotechnologie
Published: 2024/10/14
Post type: Experimental study – Peer Reviewed: Yeah
Content: Summary – Definition – Introduction – Main article – Related topics
Synopsis: Specific human genes regulate key genes mutated in autism spectrum disorders (ASD). Scientists have discovered a link between two genes, present only in human DNA, and a key gene called SYNGAP1, which is mutated in intellectual disability and autism spectrum disorders. The study provides a surprisingly direct link between human brain evolution and neurodevelopmental disorders.
Why it is important: This reveals a surprising connection between genes involved in human brain evolution and developmental disorders. Researchers discovered that genes responsible for the expansion of the human brain during evolution are also associated with neurodevelopmental conditions such as autism. This finding challenges previous assumptions and provides new insights into the complex relationship between brain evolution and disorders. The study results offer new insight into the genetic basis of human brain development and may lead to better understanding and potential treatments for neurodevelopmental conditions. Disabled world.
Introduction
Human cortical neuron neoteny requires a species-specific balance of Srgap2-Syngap1 cross-inhibition at the synapse
The remarkably prolonged development of the human brain is unique among mammals and is thought to contribute to our advanced learning abilities. Interruptions in this process can explain certain neurodevelopmental diseases. Now, a team of researchers led by Prof. Pierre Vanderhaeghen (VIB-KU Leuven), together with scientists from Columbia University and the Ecole Normale Supérieure, has discovered a link between two genes, present only in human DNA, and a key gene called SYNGAP1, which is mutated in intellectual disability and autism spectrum disorders. His study, published in Neuronprovides a surprisingly direct link between human brain evolution and neurodevelopmental disorders.
Main article
The human brain stands out among mammals for its remarkably prolonged development. Synapses (critical connections between neurons in the cerebral cortex, the brain’s main center of cognition) take years to mature in humans, compared to just months in species such as macaques or mice. This extended development, also known as neoteny, is believed to be critical to the advanced cognitive and learning abilities of humans. On the other hand, it has been hypothesized that alterations in brain neoteny could be related to neurodevelopmental disorders such as intellectual disability and autism spectrum disorder.
Pierre Vanderhaeghen’s laboratory at the VIB-KU Leuven Center for Brain and Disease Research previously discovered that the prolonged development of the human cerebral cortex is mainly due to human-specific molecular mechanisms in neurons. They are now investigating these molecular timers in human neurons.
Discovering the secrets to slowing synapse development
In their latest study, the team tested the involvement of two genes, SRGAP2B and SRGAP2C, that are unique to humans. First identified by Cécile Charrier in the laboratory of Prof. Franck Polleux (Columbia University, USA), these genes have been found to slow down synapse development when artificially introduced into neurons in the mouse cerebral cortex. The question of whether these genes function in the same way in human neurons remains unanswered.
To address this, Dr. Baptiste Libé-Philippot, a postdoctoral fellow in Vanderhaeghen’s lab, knocked out SRGA2B and SRGAP2C in human neurons, transplanted them into mouse brains, and carefully monitored the development of synapses over a period of 18 months.
“We found that when these genes are turned off in human neurons, synaptic development is accelerated to remarkable levels,” says Dr. Libé-Philippot. “At 18 months, synapses are comparable to what we would expect to see in children between five and ten years old! This reflects the accelerated development of synapses seen in certain forms of autism spectrum disorder.”
Continued…
Clues to susceptibility to specific brain disorders in humans
The team then investigated the underlying genetic mechanisms behind the pronounced effects of SRGAP2B and SRGAP2C on neoteny of human neurons. They focused on the SYNGAP1 gene, an important disease gene known to be involved in intellectual disability and autism spectrum disorder.
Surprisingly, they discovered that the genes SRGAP2 and SYNGAP1 act together to control the rate of development of human synapses. Most surprisingly, they found that SRGAP2B and SRGAP2C increase the levels of the SYNGAP1 gene and can even reverse some defects in neurons lacking SYNGAP1. This finding increases our understanding of how human-specific molecules influence neurodevelopmental disease pathways, shedding light on why such disorders are more prevalent in our species.
Prof. Pierre Vanderhaeghen looks to the future:
“This work gives us a clearer picture of the molecular mechanisms that shape the slow development of human synapses. It is surprising to discover that the same genes that are involved in the evolution of the human brain also have the potential to modify the expression of diseases. “This could have important clinical relevance: more research is needed to understand how specific human mechanisms of brain development affect learning and other behaviors and how their dysregulation can lead to brain disorders could become innovative drug targets.”
Publication and financing
Neoteny of human cortical neurons requires a species-specific balance of SRGAP2-SYNGAP1 cross-inhibition at the synapse. Libé-Philippot, et al. Neuron2024.
This work was carried out in collaboration with VIB, KU Leuven, Columbia University (New York, USA) and Ecole Normale Supérieure (Paris, France). It was supported by the European Research Council, the C1 KU Leuven Internal Funds Programme, the EOS Programme, ERA-NET NEURON, the Flemish Research Foundation (FWO), the EU network NSC-Reconstruct, the Generet Foundation, the National Institutes of Health (NIH), the NOMIs Foundation and the Queen Elizabeth of Belgium Foundation.
Attribution/Source(s):
This peer-reviewed publication was selected for publication by the editors of Disabled World due to its important relevance to the disability community. Originally written by Vlaams Instituut voor Biotechnologieand published on 10/14/2024, content may have been edited for style, clarity, or brevity. For more details or clarifications, Vlaams Instituut voor Biotechnologie You can contact us at vib.be. NOTE: Disabled World does not provide any warranty or endorsement related to this item.
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Cite this page (APA): Vlaams Instituut voor Biotechnologie. (2024, October 14). Evolutionary brain genes linked to developmental disorders. Disabled world. Retrieved October 14, 2024 from www.disabled-world.com/disability/education/anthropology/evolutionary-genes.php
Permanent link: Evolutionary brain genes linked to developmental disorders: Specific human genes regulate key genes mutated in autism spectrum disorders (ASD).
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