UCLA researchers uncover how metabolism and thalamic signals steer early brain stem cells

Researchers at UCLA mapped metabolism in the developing human cortex and discovered that radial glia depend heavily on the pentose phosphate pathway; reducing glucose or blocking this pathway changes their output toward more inhibitory and later-appearing neurons. A separate investigation revealed that thalamic axons reach the cortex early and make direct contact with radial glia, a contact that boosts production of excitatory, particularly upper-layer, neurons.

The physical interaction was tied to the NRXN1 gene, whose mutations are linked to autism, as patient-derived assembloids showed altered signaling and cell-type balance. Both studies used human tissue and stem-cell-derived organoids, providing detailed resources for future research. The findings suggest that metabolic state and early neural wiring jointly shape brain development and may inform studies of neurodevelopmental disorders and brain cancers. The work was funded by numerous federal agencies and private foundations.