Two recent studies published in Cell and Science provide novel insights into the developmental decision-making processes of radial glia, a specialized stem cell type crucial for human brain formation. The Cell study, a collaboration between the labs of Aparna Bhaduri and Heather Christofk, constructed a detailed metabolic atlas of the developing human cortex using donated human tissue and brain organoids. The researchers discovered that radial glia heavily rely on the pentose phosphate pathway, which utilizes glucose to produce materials necessary for rapidly dividing cells. Manipulating glucose availability or interfering with this metabolic pathway altered the types of cells generated by radial glia, leading to increased production of inhibitory neurons and other cell types that typically emerge later in development. This finding underscores that metabolism is not merely a background process but an active influencer of stem cell fate decisions, with potential implications for understanding how maternal nutrition and metabolic disorders impact brain development.

Concurrently, the Science study, led by Claudia Nguyen, investigated the role of physical signals from the thalamus in guiding radial glia behavior. Using human stem cell-derived brain “assembloids,” the researchers observed that thalamic projections physically contact radial glia during early brain development, prompting the production of more excitatory neurons, particularly upper-layer neurons that are uniquely expanded in the human brain. This physical interaction, previously unidentified in rodents, was linked to the gene NRXN1, mutations of which are associated with autism spectrum disorder. Patient-derived assembloids carrying NRXN1 mutations exhibited altered thalamic signals that shifted the balance between stem cells and the neurons they produced, offering a potential model for studying early developmental disturbances that may contribute to neurodevelopmental disorders. Together, these studies highlight that radial glia integrate diverse environmental cues—both metabolic and physical—to orchestrate the complex cellular composition of the human cortex, advancing our understanding of normal brain development and disease vulnerability. Source

This is a summary. Read the original at sciencedaily.com.