A new theory of brain development

(Press-News.org) Your brain begins as a single cell. When all is said and done, it will house an incredibly complex and powerful network of some 170 billion cells. How does it organize itself along the way? Cold Spring Harbor Laboratory neuroscientists have come up with a surprisingly simple answer that could have far-reaching implications for biology and artificial intelligence. 

Stan Kerstjens, a postdoc in Professor Anthony Zador’s lab, frames the question in terms of positional information. “The only thing a cell ‘sees’ is itself and its neighbors,” he explains. “But its fate depends on where it sits. A cell in the wrong place becomes the wrong thing, and the brain doesn’t develop right. So, every cell must solve two questions: Where am I? And who do I need to become?” 

In a study published in Neuron, Kerstjens, Zador, and colleagues at Harvard University and ETH Zürich put forward a new theory for how the brain organizes itself during development.  

For a long time, researchers thought that cells exchanged positional information mainly through chemical signaling. This works well when dealing with just a few cells, Kerstjens explains. But the brain isn’t a few cells. It’s billions of neurons, each needing to land in exactly the right place. Chemical signals can only travel so far before fading. So, how do cells deep in a growing brain automatically ‘know’ where they are? 

The answer, Kerstjens proposes, hits close to home. “Consider how human populations spread across a country over generations,” he says. “Descendants settle near their parents, so people who share ancestry end up in neighboring regions, producing large-scale geographic structures without long-range communication. We argue that a similar principle operates in the developing brain. Cells that descend from the same progenitor tend to remain near one another.” 

To test this theory, Kerstjens and colleagues built what they call a “lineage-based model of scalable positional information.” They started with theoretical computations. Then they tested their hypothesis at scale by looking at individual and group gene expression in developing mouse brains. Finally, they confirmed their results in zebrafish, showing that the model can be used across brains of different sizes. 

Kerstjens says the model supports the notion that chemical signaling works in conjunction with a lineage-based mechanism to convey positional information. And while his work focuses on the brain, the theory could apply to many other types of developing tissue, including tumors. There may even be implications for self-replicating AI models that pass information from one generation to the next, just as our own brain cells do. 

Perhaps most importantly, showing how a single cell grows into a complex organ could help scientists solve fundamental mysteries of the mind. “The brain somehow makes us intelligent,” Kerstjens says. “How did it manage to accumulate this capability, not just over its developmental time, but over evolutionary time? This is one piece in that big puzzle.” 

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