Authors: Ellen Clarke
Researchers from Salk Institute (CA, USA) have discovered that a gene linked to psychiatric disorders is key to the development of the cerebral cortex during pregnancy. The results of the study were published recently in the journal Cell Reports.
The researchers hope that new insights into the mechanisms of the gene, termed MDGA1, could lead to better understanding of neurodevelopmental disorders.
Signs of neurodevelopmental disorders including autism, schizophrenia and bipolar disorder often take years to develop but by studying disease related genes early on in life, scientists hope to develop novel treatments and interventions to address the disorders early.
The gene MDGA1, identified by lab lead Dennis O’Leary (Salk Institute) and his team more than a decade ago, codes for a protein that is responsible for the control of neuron migration in the developing brain. MDGA1 coats the outer surface of neurons and is densely distributed within the cerebral cortex, an area of the brain integral for sensory processing, movement, planning and self-awareness.
Other research groups have also published large population-based studies implicating the gene in autism, schizophrenia and bipolar disorder. These findings allowed the team to consider their findings in the context of human disease.
In the current study, researchers investigated the role of the protein during cortical development. When Carlos Perez-Garcia (Salk Institute), lead author of the study, disabled MDGA1 in mice a little more than halfway through pregnancy when cortex development occurs, the migration of neuron precursors in the cerebral cortex was heavily disrupted. Without MDGA1 the cerebral cortex developed with approximately half of its neurons due to neuronal precursor cells dieing off prior to forming neurons.
The findings of the study suggest mutations in MDGA1 during cortical development may lead to the development of brain disorders as a result of the loss of neurons in the cortex compromising its ability to signal to other brain areas.
Subsequent experiments revealed that in the case of MDGA1 mutations, neuron precursors are prevented from sticking to one another, which is required for the cells to generate neurons.
The team now plan to study the role of MDGA1 in adulthood, as well as assessing behaviors in mice lacking the gene.
Source: Salk Institute press release