Your brain starts as a single cell and develops into a network of around 170 billion cells. Understanding how these cells organize themselves has been a long-standing question in neuroscience. Researchers at Cold Spring Harbor Laboratory have proposed a new theory that may help explain this process and could impact both biology and artificial intelligence.
Stan Kerstjens, a postdoctoral researcher in Professor Anthony Zador's lab, describes the problem as one 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 their study published in Neuron, Kerstjens, Zador, and collaborators from Harvard University and ETH Zürich introduce a new idea for how the brain organizes itself during development.
Traditionally, scientists believed that cells communicated their positions mainly through chemical signals. According to Kerstjens, this method works when there are only a few cells involved. However, since the brain contains billions of neurons that each need to find their correct position, chemical signals alone might not be enough because they lose strength over distance.
Kerstjens offers an alternative explanation based on ancestry patterns seen in human populations: "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, researchers developed what they call a "lineage-based model of scalable positional information." They began with theoretical calculations before examining gene expression patterns in developing mouse brains at both individual and group levels. Their findings were further confirmed using zebrafish models, suggesting that this approach can apply to brains of different sizes.
Kerstjens notes that while chemical signaling still plays an important role, it likely works together with lineage-based mechanisms to provide positional information during development. He also suggests that this concept could extend beyond neural tissue to other types of growing tissues such as tumors—and potentially even inform self-replicating AI systems that transfer information between generations like biological cells do.
Understanding how complex organs like the brain grow from single cells may help scientists address basic questions about consciousness and cognition.
