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Kuo-Fen Lee

 

Kuo-Fen Lee

Kuo-Fen Lee

Professor
Clayton Foundation Laboratories for Peptide Biology

"Communication happens at many different levels and in many different ways but they all have one thing in common: They need underlying hardware to convey the information. I am interested in how the nervous system wires up the body during embryonic development so the brain can send and receive signals."

A newborn baby moves, breathes, and cries in part because a network of motor neurons carries signals from its brain and spinal cord to muscles throughout its body. Motor neurons, which cause muscle fibers to contract, connect via neuromuscular synapses that coordinate communication between nerves and the muscles they control. Scientists had long suspected that chemical cues released from growing nerve cells in the developing embryo helped point the way to the birthplace of synapses. By monitoring the clustering of neurotransmitter receptors—specialized molecules that can receive chemical messages released by neurons— on muscle cells, a generally accepted indicator of impending neuromuscular synapse formation, Lee and his team found that the opposite is true. Each muscle cell in a two-week-old developing embryo has prepared for the arrival of its motor neurons by creating sites for many potential synapses along its length. But three weeks after conception, all the sites have disappeared except those that have successfully connected with a newly arrived motor neuron and formed fully functioning synapses.

Lee and his colleagues then wanted to know how the embryo weeds out the potential sites that are not needed. The answer is crucial to ensure that nerves regenerated after spinal cord injuries make proper connections with muscle cells.

Using mice as a model, they discovered that while the muscles prepare the ground, the nerves themselves control and nurture the formation of synapses. As they grow toward muscle cells, they release a powerful chemical messenger from the tip. Called acetylcholine, this neurotransmitter "edits out" the potential sites on the muscle cells that are not destined to connect to a nerve. Acetylcholine works in tandem with another chemical produced by nerve calls, called agrin. Where the end of the nerve touches a muscle cell, agrin overcomes the "editing" effect of acetylcholine. Farther away, agrin levels are not high enough to cancel out the overpowering influence of actylcholine, and the redundant synaptic sites are dismantled. These findings illustrate that neurotransmitters may control the sculpting of the very synapses that will serve as the messengers.

Lab Photo

Left to right:
Michelle Lee, Bertha Dominguez, Fred DeWinter, Kuo-Fen Lee, Tsung-Chang Sung, Andrew Chen, Zhijiang Chen

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Kuo-Fen Lee

Faculty

Kuo-Fen Lee

Kuo-Fen Lee

Professor
Clayton Foundation Laboratories for Peptide Biology

Kuo-Fen Lee, a professor in the Clayton Foundation Laboratories for Peptide Biology, studies the genes and molecules that guide brain cell development. He has considerable expertise in producing mice to study the effects of specific genes on nervous system function. His lab focuses on how disruptions in development and maintenance of nerve cells and their supporting cells can contribute to neurodegenerative diseases, such as Alzheimer's disease, neuroendocrine diseases, such as anxiety, and neuromuscular diseases.

Lee and his lab use gene "knock-out" technology to delete or alter the genes of mice models to observe the physiological effects. This may speed up by decades the discovery of how abnormalities occur in how brain cells communicate with each other. The ultimate goal of this work is to develop therapies to prevent brain cell death and treat disorders.

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