Human-Specific Genes Link Brain Development and Autism.

New Study Finds A groundbreaking study reveals a connection between two human-specific genes and the SYNGAP1 gene, which is associated with intellectual disabilities and autism spectrum disorders (ASD).

The genes, SRGAP2B and SRGAP2C, appear to delay synapse development—a key process in the prolonged brain growth that distinguishes humans from other mammals. Researchers found that turning off these genes in human neurons accelerates brain connectivity, mimicking changes often observed in neurodevelopmental conditions.

Key Findings SRGAP2B and SRGAP2C:

These human-specific genes slow synapse development, a feature thought to enhance learning in humans.SYNGAP1 Gene: Linked to intellectual disability and autism, it interacts with SRGAP2 genes to regulate the speed of brain connectivity.

Gene Knockout Study: Disabling SRGAP2B and SRGAP2C in human neurons accelerated synapse formation, similar to patterns seen in some individuals with ASD.A Window into Human Brain EvolutionThe study, conducted by a team led by Prof. Pierre Vanderhaeghen from VIB-KU Leuven in collaboration with Columbia University and Ecole Normale Supérieure, offers a deeper understanding of how human brain development differs from that of other mammals. Unlike species such as mice or macaques, where synapse maturation takes only months, human synapses mature over several years, supporting advanced cognitive abilities.

However, this prolonged development—also known as neoteny—can make humans more susceptible to neurodevelopmental disorders when disrupted.Experimental BreakthroughTo explore the role of SRGAP2B and SRGAP2C, Dr. Baptiste Libé-Philippot, a postdoctoral fellow in Vanderhaeghen’s lab, switched off these genes in human neurons transplanted into mouse brains. Over 18 months, the researchers observed that synapses developed faster, reaching a level comparable to those in human children aged 5 to 10.

This accelerated development mirrors patterns found in some forms of autism.Genetic Mechanisms and Disease PathwaysThe team discovered that SRGAP2 genes regulate the expression of SYNGAP1, a gene crucial to synapse function. Interestingly, SRGAP2B and SRGAP2C can even reverse some neuronal defects caused by SYNGAP1 mutations, providing insights into potential therapeutic avenues for neurodevelopmental disorders.Implications for Future Research“This study helps us understand how human-specific genes shape the slow development of synapses, but also how their dysregulation can lead to brain disorders,” said Prof. Vanderhaeghen.

The findings suggest that molecules involved in brain evolution could become innovative drug targets to treat conditions like autism and intellectual disabilities.Collaborative Effort and SupportThe research was a collaborative project between VIB, KU Leuven, Columbia University, and Ecole Normale Supérieure.

It was funded by multiple organizations, including the European Research Council, the National Institutes of Health (NIH), and the Research Foundation Flanders (FWO).This study not only enhances our understanding of human brain development but also opens new doors for exploring how genetic pathways could inform treatments for neurodevelopmental disorders.