The cerebral cortex underlies the brain’s highest cognitive functions. Its extraordinary structural and functional complexity depends on both the total number of neurons and the diversity of neuronal cell types. The human cerebral cortex contains approximately 16 billion neurons, broadly classified into glutamatergic excitatory neurons and γ-aminobutyric acid (GABA)–ergic inhibitory neurons. Beyond this basic division, hundreds of neuronal subtypes have been identified based on differences in morphology, connectivity, electrophysiological properties, and gene expression.
Inhibitory neurons function as the brain’s “braking system”, maintaining the intricate balance between excitation and inhibition, without which normal information processing would be disrupted and lead to various neurological and neurodevelopmental disorders, including epilepsy and autism spectrum disorder. During evolution, the expansion of the human cerebral cortex has been accompanied by a coordinated increase in both the number and proportion of inhibitory neurons. Nevertheless, it remains unresolved how diverse inhibitory neuron types are generated in an orderly manner during human brain development, and how the human brain achieves such a pronounced expansion in inhibitory neuron number and proportion.
On January 15, 2026, a study published in Science reports the identification of a previously uncharacterized neural stem cell population in the developing human brain—subventricular zone radial glial cells (SVZ RGCs). The study, co-led by Dr. Da Mi (Tsinghua University) and Dr. Lan Zhu (Peking Union Medical College Hospital), shows that these cells continuously generate inhibitory neurons and glial cells throughout human gestation, sustaining inhibitory neurogenesis over an extended developmental period and substantially increasing both the number and diversity of inhibitory neurons in the human cerebral cortex. These findings provide critical insight into the evo-devo of human cortical development. Given the close link between inhibitory neuron dysfunction and disorders such as epilepsy and autism spectrum disorder, the identification of this novel stem cell population also opens new directions for future research into disease mechanisms and potential interventions.
Research Highlight #1: Evolutionarily Distinct Neural Stem Cell Type
In mammals, cortical inhibitory neurons primarily originate from the medial ganglionic eminence (MGE) in the ventral telencephalon. Using a combination of spatial transcriptomics and single-cell RNA sequencing, the research team generated a comprehensive molecular and cellular atlas of the human MGE spanning gestational weeks 9 to 39. This analysis led to the identification of SVZ RGCs, a previously unrecognized neural stem cell population in the human fetal MGE. SVZ RGCs are distinct from previously described progenitor types in their molecular signatures, spatial distribution, and patterns of cell division. Cross-species comparative analyses revealed broad presence of SVZ RGCs in primates but found no counterpart in the mouse brain. In addition, SVZ RGCs continuously produce inhibitory neurons and glial cells during human fetal development, establishing them as a key cellular source underlying the expansion anddiversification of inhibitory neurons in the human brain.
Research Highlight #2: Spatiotemporal Landscape of the Human MGE Reveals Core Principles Governing Inhibitory Neuron Diversity
The remarkable diversity of neurons in the human brain is fundamental to advanced cognitive function. A longstanding question in neuroscience is how such diversity arises in a precise and reproducible manner from a relatively limited pool of neural progenitor cells. To this end, the researchers systematically mapped the spatiotemporal landscape of neurogenesis in the human fetal MGE. This dataset revealed highly compartmentalized progenitor domains within the human MGE, each corresponding to specific inhibitory neuron lineages. It also demonstrated strict temporal pattern of inhibitory neurogenesis: early in development, neurogenesis is dominated by progenitor domains located in the ventricular zone (VZ), including the LHX8/ISL1⁺ and the NR2F1/NR2F2⁺ populations; at later stages, neurogenesis shifts predominantly to the subventricular zone (SVZ), where EPHA5/MEF2C⁺, CRABP1/ANGPT2⁺, and LHX6/NFIA⁺ progenitor domains become the primary sources of newborn neurons. These findings uncovered core principles governing inhibitory neuron diversification: the identity of certain inhibitory neuron subtypes is specified at the progenitor stage and is tightly constrained by both their spatial origin and developmental timing.
