Target cells found to play active role in synapse formation

November 02, 2000

CHAMPAIGN, Ill. - When axons connect with target cells, synapses form - a pivotal brain development stage that allows for such things as muscle coordination, learning and memory. The outward reaching fingers of axons, called filopodia, have been thought to be the driving force for these connections. However, a new view is emerging at the University of Illinois.

Using a scanning electron microscope and green fluorescent protein (GFP) to coat target cells, in this case live cell muscle membranes from Drosophila, UI researchers detected similar axon-like fingers. Filopodia extending from axons - the communicating arms of neurons - are well documented and thought to be the reaching, seeking fingers that latch on to the receptors of target cells such as muscles.

In the October issue of Nature Neuroscience, the UI scientists documented their findings, which have attracted growing interest from neuroscientists learning of the work at professional meetings.

"The idea has been that pre-synaptic axons were doing all the searching, and muscles were just sitting there very passively," said Akira Chiba, a professor in the UI department of cell and structural biology and neuroscience program. "The dynamics of the interaction on the post-synaptic side has been poorly documented. What we have shown is that the muscle side has long processes just like axons, if not more. They are dynamic, long and numerous."

To differentiate the newly found thread-like processes of muscles from the neuronal filopodia, Chiba and co-authors Sarah Ritzenthaler, a UI doctoral student, and Emiko Suzuki of the University of Tokyo, have labeled them as myopodia.

"The myopodia are there, and they are very dynamic," said Ritzenthaler, who has presented the work at several meetings. "They are just like neuronal filopodia in their activity and in their cellular components."

"This research has changed my own bias and that of probably many other people with regard to what is happening where and when in synaptogenesis," Chiba said. "So far, we are raising the status of the activity on the post-synaptic side to essentially the same level as that of the presynaptic side."

The genetically engineered GFP allowed researchers to coat the membranes of both live axons and live muscle cells without destroying them. The technique, Chiba said, allowed microscopes to zoom in on the difficult-to-capture interaction of cells communicating in the central nervous system.

Time-lapse photography clearly showed the myopodia, only in the presence of axons, appearing to cluster to the filopodia, as if building a lifeline to a ship at sea. During this interaction, Chiba said, the two sides are matchmaking, realizing their compatibility. "If this interaction does not occur properly, there is no synapse," he said. "Muscle does not become connected with the brain."
The research was funded by Japan's Core Research for Evolutional Science and Technology program, U.S. National Institutes of Health, the National Science Foundation, and the Lucille P. Markey Charitble Trust.

University of Illinois at Urbana-Champaign

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