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Brain development is a complex process involving the activation of specific genes, with genetic mutations potentially disrupting this delicate balance. MEIS2, a protein discovered by Christian Mayer and his team, was found to play a crucial role in activating genes necessary for the formation of inhibitory projection neurons. These neurons are essential for motion control and decision-making, and a mutation in MEIS2, seen in patients with severe intellectual disability, was found to impede these processes. This study enhances our understanding of brain development and the consequences of genetic mutations.

Nerve cells originate from a limited number of progenitor cells, and the activation of specific genes determines the developmental path a cell will take. Researchers like Christian Mayer are working to unravel the complexities of neuron development. The formation of inhibitory neurons, which produce the neurotransmitter GABA, was studied by Mayer’s team. Inhibitory neurons can act locally or send long-range axons to different brain regions, contributing to various brain functions. MEIS2 was found to assist in activating genes required for precursor cells to become projection neurons, influencing the decision between becoming an interneuron or projection neuron.

MEIS2 collaborates with another protein, DLX5, in the development of projection neurons. When MEIS2 is not functioning correctly, more precursor cells turn into interneurons instead of projection neurons. A variant of MEIS2 found in patients with intellectual disabilities was tested in experiments, revealing its failure to induce genes necessary for projection neuron formation. Understanding the role of genes like MEIS2 in brain development is crucial as mutations can lead to neurodevelopmental disorders and a range of symptoms affecting various body parts.

Genes like MEIS2 activate specific sets of enhancers, regulatory elements in the genome that control gene activation. In the brain, MEIS2 and DLX5 work together to activate enhancers that induce the expression of projection neuron genes. Understanding the molecular interactions between proteins encoded by risk genes for neurodevelopmental disorders, such as MEIS2, can provide valuable insights into the biological mechanisms underlying these disorders. Large-scale sequencing studies have identified risk genes for such disorders, highlighting the importance of further research on molecular interactions to deepen our understanding.

The importance of genes like MEIS2 in brain development and neurodevelopmental disorders is evident in the diverse range of symptoms observed in patients with mutations in these genes. The intricate control mechanisms by genes in different parts of the body highlight the complexity of human development. Enhancers and other regulatory elements in the genome play a crucial role in gene activation, acting as switches that determine when and where genes are expressed. Future studies that focus on understanding the specific roles of genes like MEIS2 in different biological processes will contribute to a comprehensive understanding of brain development and associated disorders.

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