【Key Points】
- The research revealed how a large number of neurons come together to form "columnar structures," which are the functional units of the brain.
- The team developed an antibody capable of detecting the "on/off" state of Ephrin, which acts as a molecular switch, and "visualized" the state changes inside and outside the column.
- We demonstrated that when Ephrin is phosphorylated (switched on), it changes the "arrangement and boundaries" of neurons and promotes the formation of precise neuronal circuits.
- The molecular switch mechanism relies on an unusual "reverse signaling" mechanism, a new discovery that could lead to the elucidation of the principles of higher-order wiring design in the brain.
A collaborative research group led by Professor Makoto Sato of Institute for Frontier Science Initiative, Kanazawa University, has elucidated the molecular mechanism that controls the formation of the column structure, the functional unit of the brain, using fruit flies, a representative model organism for brain research.
The brain is composed of countless neurons, which are organized in a highly structured manner; rather, a column structure is formed when a large number of neurons gather in a regular pattern. Column structures are known as "functional units" of the brain and are important structures that support complex brain functions. In this study, we aimed to elucidate the entire mechanism of how the arrangement and boundaries of neurons are precisely controlled by correctly distinguishing between the inside and outside of the column.
The research group focused on Ephrin, which acts as a molecular switch, and developed an antibody to distinguish its "on/off" state. This antibody successfully "visualized" the state change of Ephrin inside and outside the column for the first time in the world (see figure). Furthermore, as a result of verification through a combination of various experiments, it was demonstrated that phosphorylation (switch-on) of Ephrin changes the arrangement and boundaries of neurons and promotes the formation of precise neural circuits.
Ephrin is an important molecule present not only in flies but also in mice and humans. The brain wiring mechanism revealed in this study is likely to be common to all animals across evolution, and is expected to have a significant impact on human brain development, regenerative medicine, and research on neurological diseases in the future.
The results of this research were published in the online edition of the American scientific journal Science Advances on August 13, 2025 (U.S. time).
Click here to see the press release【Japanese only】
Journal：Science Advances
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