Mathematical laws underlying brain development have been identified.

Stanford researchers identified a pattern that regulates the development of brain cells or neurons using sophisticated microscopy and mathematical modeling. Similar principles may govern the growth of other cells in the body, and knowing them may be critical for effectively designing artificial tissues and organs.

Their discovery, published in Nature Physics, is based on the fact that the brain includes many distinct types of neurons and that every job requires many types of functioning together. The researchers hoped to find the unseen development patterns that allow the proper kind of neurons to organize themselves into the correct locations to form a brain.

“How can cells with complementary tasks organize themselves to form a working tissue?” said research co-author and bioengineering assistant professor Bo Wang. “We opted to examine a brain to address that question since it was widely thought that the brain was too complicated to have a simple patterning rule. We were taken aback when we realized there was, in fact, such a rule.”

This shows neurons
Stanford researchers used advanced microscopy and mathematical modeling to discover a pattern that governs the growth of neurons in the flatworm brain, shown here. Using this technique, they hope to find patterns that guide the growth of cells in other parts of the body in order to pave the way to bioengineer artificial tissues and organs. The image is credited to Wang Lab.

The brain they selected to study belonged to a planarian, a millimeter-long flatworm that can regenerate a new head following amputation every time. First, Wang and a graduate student in his lab, Margarita Khariton, employed fluorescent dyes to label distinct kinds of neurons in the flatworm. They then used high-resolution microscopes to take photos of the entire brain – glowing neurons and all – and examined the patterns to see if they could deduce the mathematical rules that guided its creation.

They discovered that each neuron is surrounded by approximately a dozen neighbors who are identical to it, but that there are different types of neurons scattered among them. Because of this unusual configuration, no one neuron rests flush against its twin while allowing different types of complimentary neurons to be close enough to work together to perform tasks.

Co-authors of the study Jian Qin, an assistant professor of chemical engineering, and postdoctoral scholar Xian Kong created a computational model to demonstrate that this complex network of functional neighborhoods is caused by neurons’ tendency to pack together as closely as possible without being too close to other neurons of the same type.

The fundamental premise is straightforward: tissue engineers aim to drive stem cells, the strong, all-purpose cells from which all cell types arise, to differentiate into the numerous specialized cells that comprise a liver, kidney, or heart. However, if the heart is to beat, scientists will need to organize those different cells into the proper patterns.

While neuroscientists may someday use this technology to investigate neural patterning in the human brain, Stanford researchers feel it will be more beneficial in the growing area of tissue engineering.

Chromatic’ Neuronal Jamming in a Primitive Brain, Margarita Khariton, Xian Kong, Jian Qin, Bo Wang

Published: March, 2020

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