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Study maps autism-linked protein in neurodevelopment.

Signs of autism, schizophrenia and bipolar disorder often take years to manifest. Studying suspect disease genes in the brain early in life could prove valuable in the development of new treatments or interventions.  Now, a study from researchers at the Salk Institute shows that a gene linked to mental disorders helps lays the foundation for a crucial brain structure during prenatal development.  The team state that their findings reveal new mechanistic insights into the gene, known as MDGA1, which may bring a better understanding of neurodevelopmental disorders in people.  The opensource study is published in the journal Cell Reports.

Earlier studies from the group identified MDGA1, which codes for a protein that influences neuron migration in the developing brain. Coating the outer surfaces of neurons, it was found that MDGA1 is particularly abundant in the cerebral cortex, a six-layered area of the brain needed to process information from the five senses and coordinate movement, as well as to be self-aware and plan ahead.  Large population-based studies from other institutions implicated the newly-discovered gene in autism, schizophrenia and bipolar disorder.  Therefore, the current study investigates the protein’s role in early brain development, when the foundation of a proper, six-layer cortex is being laid.

The current study shows that when the gene is disabled in mice a little more than halfway through pregnancy the neuron precursors in the cerebral cortex migrate to the wrong places in the brain. Results show that when these cells die off before they can become neurons, without MDGA1, the cerebral cortex loses about half its neurons.  Data findings show that when MDGA1 is mutated it prevents neuron precursors from sticking to one another, which is critical for those cells to divide and generate neurons.

The team surmise that their findings suggest that mutations in MDGA1 while the cortex is developing could produce snowball effects leading to the development of brain disorders. They go on to add that the severe depletion of neurons in the cortex strongly compromises its ability to communicate with other brain areas.  For the future, the researchers plan to continue to examine the role of MDGA1 earlier in neurodevelopment and also during adulthood, as well as assess behaviours of mice lacking the gene.

Source: Salk Institute

The autism-linked protein MDGA1 (red) is found in the zones of the brain that give rise to new neurons (green).  Credit: Salk Institute.
The autism-linked protein MDGA1 (red) is found in the zones of the brain that give rise to new neurons (green). Credit: Salk Institute.

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