Summary: Researchers have found a link between two human-specific chromosomes and the protein SYNGAP1, a factor in intellectual disabilities and autism spectrum disorders. These genes, SRGAP2B and SRGAP2C, slow down junction growth, a cornerstone of persistent head development thought to improve learning in humans. Researchers observed an increase in brain communication development by turning off these alleles in human neurons, mimicking changes seen in some developmental problems.
This finding suggests that the genes that control the evolution of the human mind may also affect the risk of developing brain diseases. Future research will examine how these genes affect learning and whether they could lead to novel therapies. The investigation provides important insight into the causes of some of the more prevalent neurological problems in people.
Important Information:
- SRGAP2B and SRGAP2C chromosomes slow down neuron growth in people.
- Turning off these genes in cells speeds up brain communication, reflecting changes in dementia.
- These human-specific genes work with SYNGAP1, linked to philosophical disability and dementia.
Origin: VIB
The remarkable, protracted development of the human brain is thought to be a sign of how advanced our brains are. This process’s variations may contribute to the development of some developmental disorders.
A team of researchers led by Prof. Pierre Vanderhaeghen (VIB-KU Leuven ), as well as Columbia University and Ecole Normale Supérieure, have now identified a link between a crucial gene, SYNGAP1, which is mutated in intellectual disability and autism spectrum disorders, and two genes that are unique to human DNA.
Their research, published in , Neuron,  , provides a remarkably strong link between individual brain evolution and developmental disorders.
The human mind is unique among primates because of how quickly it develops. In humans, synnapses, which are crucial connections between the cerebral cortex’s main hub for consciousness, take years to mature, compared to only months in varieties like macaques or mice.
This prolonged development, also known as neoteny, is thought to be key to mankind ‘ developed cognitive and learning skills.
On the other hand, it has been suggested that mind neoteny problems may be related to neurodevelopmental disorders like autism and intellectual retardation.
The VIB-KU Leuven Center for Brain & Disease Research lab’s Pierre Vanderhaeghen recently discovered that the long-term development of the human brain brain is primarily a result of neuronal-specific chemical methods. They are currently looking into these molecular settings in individual neurons.
Unlocking the strategies to decrease junction development
In their latest study, the group tested the presence of two chromosomes, SRGAP2B and SRGAP2C, which are unique to humans. These genes were first discovered by Cécile Charrier in Prof. Franck Polleux’s ( Columbia University, USA ) lab, and have since been shown to slow down synapse development when artificially introduced into mouse cerebral cortex neurons. The reoccurring of the topic of whether these genes function in the same way in human cells has remained unresolved.
To solve this, Dr. Baptiste Libé-Philippot, a Postdoctoral Fellow in the Vanderhaeghen test, switched off SRGA2B and SRGAP2C in human cells, transplanted them into keyboard brains, and carefully monitored neuron growth over an 18-month time.
” We discovered that when you turn off these chromosomes in human cells, neural development speeds upwards at extraordinary rates”, says , Dr. Libé-Philippot.  ,
The connections are similar to what we would anticipate in children between the ages of five and ten by 18 months! This reflects the rapid neuron growth that some autism spectrum disorders exhibit.
Signs to human-specific mental illness susceptibility
The crew then examined the core genetic factors that explain the prominent effects of SRGAP2B and SRGAP2C on neoteny in human synapse. They concentrated on the SYNGAP1 gene, an important disease gene implicated in autism and intellectual disability.
Remarkably, they discovered that the SRGAP2 and SYNGAP1 genes act together to control the speed of human synapse development. Most strikingly, 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 expands our understanding of how neurodevelopmental disease pathways are influenced by human-specific molecules, revealing why these conditions are more common in our species.
Prof. Pierre Vanderhaeghen , is looking forward to the future:  ,” This work gives us a clearer picture of the molecular mechanisms that shape the slow development of human synapses.
It is amazing to learn that the same genes that control the human brain’s evolution also have the power to affect the expression of specific brain diseases.
More research is required to understand how human-specific mechanisms of brain development affect learning and other behaviors, and how dysregulation can result in brain disorders, according to Dr. Jain. It becomes possible that some novel gene products that are human-specific could turn into novel drug targets.
This work was performed in collaboration with VIB, KU Leuven, Columbia University ( NY, US), and Ecole Normale Supérieure ( Paris, France ).
Funding: It was supported by the European Research Council, the C1 KU Leuven Internal Funds Programme, the EOS Programme, ERA-NET NEURON, Research Foundation Flanders ( FWO ), the EU network NSC-Reconstruct, the Generet Foundation, the National Institutes of Health ( NIH), the NOMIs Foundation, and the Belgian Queen Elizabeth Foundation.
About this ASD, genetics, and neurodevelopment research news
Author: India Jane Wise
Source: VIB
Contact: India Jane Wise – VIB
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Human cortical neuron neoteny requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition at the synapse” by Pierre Vanderhaeghen et al. Neuron
Abstract
Human cortical neuron neoteny requires species-specific balancing of SRGAP2-SYNGAP1 cross-inhibition at the synapse
Human-specific ( HS) genes have been implicated in brain evolution, but their impact on human neuron development and diseases remains unclear.
Here, we study SRGAP2B/C, two HS gene duplications of the ancestral synaptic gene SRGAP2A, in human cortical pyramidal neurons ( CPNs ) xenotransplanted in the mouse cortex.
Downregulation of SRGAP2B/C in human CPNs led to strongly accelerated synaptic development, indicating their requirement for the neoteny that distinguishes human synaptogenesis.
SRGAP2B/C genes promoted neoteny by reducing the synaptic levels of SRGAP2A, thereby increasing the postsynaptic accumulation of the SYNGAP1 protein, encoded by a major intellectual disability/autism spectrum disorder ( ID/ASD ) gene.
Combinatorial loss-of-function experiments , in , vivo , revealed that the tempo of synaptogenesis is set by the reciprocal antagonism between SRGAP2A and SYNGAP1, which in human CPNs is tipped toward neoteny by SRGAP2B/C.
Thus, HS genes can influence the phenotypic expression of genetic mutations that cause ID/ASD by controlling the expression of human synaptic neoteny.
