How progenitor cells in the developing brain divide to make neurons, how the cortex is built inside-out along radial glia, and what happens when migration goes wrong.
Development & Plasticity
Advanced
Neurogenesis and Neural Migration
The Editors
December 18, 2025
2 min read
In plain English
Before birth, special stem cells lining the brain's inner surface divide over and over to make neurons. The new neurons then crawl outward along guide fibres to their places in the cortex, building it from the inside out. Errors in this process can cause malformations, epilepsy and intellectual disability.
Advanced level: The detailed machinery — ions, receptors, circuits and methods. Read the linked concepts first.
Concepts to know first
Where neurons come from
The cortex is generated from a layer of dividing cells next to the ventricles, the ventricular zone. The key progenitors are radial glial cells, which stretch from the inner surface of the developing brain all the way to its outer surface. They divide asymmetrically: each division produces another radial glial cell plus either a neuron or an intermediate progenitor that divides a few more times. In primates, and especially humans, an additional zone of outer radial glia greatly expands production — thought to be one reason the human cortex is so large.
Inside-out
Newborn neurons climb along the long fibres of radial glia like rock climbers on a rope. The first neurons to arrive form the deepest layers; later-born neurons migrate past them to form progressively more superficial layers. The six-layered cortex is therefore built inside-out. A protein called reelin, secreted at the cortex's surface, helps tell migrating neurons where to stop. Inhibitory interneurons take a different route, migrating sideways (tangentially) from the ganglionic eminences at the base of the forebrain.
When migration fails
Disrupted migration causes neuronal migration disorders. In lissencephaly ("smooth brain"), caused for example by mutations in the LIS1 gene, the cortex lacks normal folds and layers, causing severe disability and epilepsy. In periventricular heterotopia, clumps of neurons never leave the ventricle wall. Such malformations are a common cause of drug-resistant epilepsy. Too little proliferation causes microcephaly — as seen when the Zika virus, which infects neural progenitors, swept through Brazil in 2015–2016.
Growing brains in a dish
Since 2013, scientists have grown brain organoids — small three-dimensional clusters of neural tissue derived from human stem cells — that recapitulate early steps of cortical development, including radial glia and layer formation. They are valuable for studying conditions like Zika-related microcephaly, though they lack blood vessels, inputs and the full organisation of a real brain.
Everyday examples & things to try
Analogy
Building a stadium from the field up
Imagine filling a stadium where every new spectator must walk past those already seated to reach a higher row. The first arrivals sit at the bottom, the last at the top. The cortex fills its layers the same way — the newest neurons climbing past the old ones on radial glial 'ladders'.
Key takeaways
- Radial glial cells are the main neural progenitors and also act as migration scaffolds.
- The cortex is built inside-out: early-born neurons deep, late-born neurons superficial.
- Migration and proliferation errors cause lissencephaly, heterotopias and microcephaly.
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