Before birth, the human brain builds itself through a complex series of cellular decisions driven by specialized stem cells called radial glia. These cells create the massive pool of neurons and support cells that make up the cerebral cortex—the seat of human thought, memory, and language—and drive its vast expansion compared to other species. Though most vanish before birth, radial glia can reappear in brain cancers for reasons still unknown. Now, two studies published in Cell and Science reveal that these stem cells decide what to become by actively responding to metabolic changes and physical contact from distant brain regions. Here’s all you need to know about.Metabolism directs stem cell choicesIn the Cell study, led by Jessenya Mil and Jose Soto from the labs of Aparna Bhaduri and Heather Christofk at UCLA, researchers created a metabolic map of the developing human cortex using donated tissue and stem-cell-derived brain organoids. They discovered that metabolism is far more than a passive background process; it directly controls stem cell decisions. Radial glia rely heavily on the pentose phosphate pathway, which uses glucose to fuel rapid cell division. When researchers reduced available glucose or blocked this metabolic pathway, the radial glia shifted their output. Instead of their typical cell production, they began generating more inhibitory neurons and cell types that normally appear much later in development. This insight provides a baseline to explore how maternal nutrition and metabolic disorders impact early brain growth.Early physical signals from the ThalamusThe Science study, led by Claudia Nguyen in Bhaduri’s lab, investigated how signals from the thalamus—a deep structure that relays sensory information—shape the cortex. Long, wire-like fibers from the thalamus extend to the cortex during development, reaching it far earlier than needed to establish final neural connections. Using stem-cell-derived “assembloids,” UCLA researchers discovered why these fibers arrive so early: they physically touch radial glia while the brain is still forming. This direct contact prompts the stem cells to generate more excitatory neurons, particularly upper-layer neurons that are heavily expanded in humans. According to Bhaduri, this physical contact mechanism likely does not exist in rodents.Connecting Autism genes and stem cell behaviorThe team linked this physical interaction to NRXN1, a gene involved in establishing neural connections and previously tied to autism spectrum disorder. When scientists built assembloids using patient-derived cells with an NRXN1 mutation, the altered thalamic signals disrupted the typical balance between stem cells and the neurons they created. This offers a new path to study how early developmental disruptions influence cortex formation.Radial glia don’t build a brain in a vacuum. Everything around them—from the nutrients they absorb to physical nudges from neighboring brain regions—tells these stem cells what to become next.Thanks to lab-grown brain organoids, researchers can finally watch these uniquely human cellular behaviors happen in real time without relying solely on animal models. Pinpointing these signals gives scientists a much clearer picture of normal brain growth, why certain neurodevelopmental disorders arise, and how these same stem cell programs get hijacked later in brain cancer.