Researchers at UT Southwestern Medical Center have uncovered that during a specific stage of neurodevelopment, neural cells produce fewer ribosomes, which are essential for protein synthesis.

Led by Dr. Michael Buszczak, the research team, which included international collaborators, aimed to understand the implications of this ribosome decline during early brain development.

This reduction in ribosome levels occurs during neuroepithelial differentiation, making developing brain cells particularly vulnerable to changes in ribosome production.

Utilizing organoid models, the researchers found that mutated cells formed smaller brain organoids with higher cell death rates compared to nonmutated cells by day 15 of development.

The study revealed that both organoid types exhibited decreased ribosome production, but those with AIRIM mutations showed an even greater reduction, leading to lower levels of critical proteins necessary for cell survival and differentiation.

In a breakthrough, the team enhanced mTOR activity, a protein that promotes ribosome production, successfully 'rescuing' the mutated cells and allowing them to develop similarly to nonmutated cells.

Dr. Buszczak suggested that targeting ribosome deficiencies could lead to interventions that might treat certain neurodevelopmental disorders before birth, potentially alleviating symptoms associated with these genetic conditions.

The findings, published in Nature Cell Biology, emphasize the critical role of ribosome biogenesis in neurodevelopmental disorders characterized by severe intellectual disabilities and sensory impairments linked to mutations in the AIRIM gene.

The researchers plan to investigate whether similar declines in ribosome levels are present in other neurodevelopmental disorders caused by genetic mutations affecting ribosome-related genes.

Overall, this research highlights the significance of ribosome production during early neurodevelopment and its potential implications for understanding various neurodevelopmental disorders.