How the Developing Human Brain Listens to Food and Touch: New UCLA Insights

When a human baby is still just a bundle of cells, a handful of stem cells called radial glia are already busy making choices that will shape every thought, memory and word the child will ever have. These cells are something of a master‑builder, churning out billions of neurons and support cells that stack up into the cerebral cortex – the brain’s outer layer where consciousness lives.

"Radial glia are the coolest cells that have ever existed," enthuses Aparna Bhaduri, an assistant professor of biological chemistry at UCLA’s David Geffen School of Medicine. She and her team have spent years watching these cells in petri dishes and, more recently, in clever three‑dimensional “assembloids” that mimic tiny pieces of a developing brain. Their newest work, reported in Cell and Science, reveals that radial glia don’t decide in a vacuum. Instead, they listen to two very different kinds of instructions – one that comes from the nutrients they consume, and another that arrives via physical touch from a neighboring brain region.

Metabolism as a decision‑maker

In the first study, Bhaduri’s lab teamed up with Heather Christofk’s group to map the metabolic landscape of the human cortex. By comparing donated fetal tissue with stem‑cell‑derived brain organoids, they assembled a detailed atlas of how glucose and related pathways are used during development. One pathway, the pentose‑phosphate shunt, stood out. It churns glucose into building blocks that rapidly dividing cells need.

When the researchers dialed down glucose or knocked out key enzymes in that pathway, the radial glia didn’t just slow down – they changed their output. The cells produced a higher proportion of inhibitory neurons and other later‑born cell types, as if the metabolic shortage nudged them toward a different developmental script.

"What was surprising is that metabolism isn’t just a passive backdrop," Bhaduri notes. "It can actively steer stem‑cell fate." This discovery opens a window onto how maternal diet, diabetes or other metabolic stresses might ripple into the developing brain, potentially influencing risk for neurodevelopmental disorders.

A physical hello from the thalamus

The second paper took a very different angle. Using “assembloids” that fuse cortical organoids with those derived from the thalamus – the deep‑brain hub that shuttles sensory information – the team watched what happened when thalamic axons reached the cortical surface. Contrary to the old belief that those long fibers only form mature connections later, they found the thalamic projections actually touch radial glia very early on.

This tactile handshake appears to tell the radial glia to crank out more excitatory, upper‑layer neurons – the very cell types that have expanded dramatically in humans compared with other mammals. The contact is mediated, at least in part, by the gene NRXN1, a protein best known for wiring synapses and already implicated in autism.

"We discovered a physical link that hadn’t been seen before," says Bhaduri. "It’s a kind of early‑stage wiring that seems to be uniquely human." The finding suggests that the thalamus is not just a passive messenger but an active sculptor of cortical architecture.

Together, these two studies recast the radial glia’s environment – its diet and its neighbors – as dynamic teachers that help build the brain’s astonishing cellular diversity. Understanding those cues could eventually help scientists devise ways to repair faulty development or even curb the re‑appearance of radial‑glia‑like cells in brain cancers.

For now, the work reminds us that the growing brain is a conversation between chemistry and connection, a duet of nutrients and touch that makes us, quite literally, who we are.