|Pruning Neuronal Trees
|Confocal fluorescent reconstruction of two PVD
By studying the small (1 mm) roundworm C. elegans, a Technion-led international research team has discovered how tree-like nerve structures are formed and maintained. Published online in the May 6th issue of Science Express, this breakthrough may have applications in the treatment of neurodegenerative diseases and in the repair of nerve damage.
neurons that form reproducible branching trees
that look like menorahs
Prof. Benjamin Podbilewicz of the Technion Faculty of Biology reports that while biologists have known for years that many neurons form complicated tree-like structures, it was not understood how the neurons form and maintain them. To unravel this mystery, his PhD student Meital Oren-Suissa, 30, and the research team first examined the dynamic development of two mechanoreceptor neurons known as PVDs required for reception of strong mechanical stimuli in
C. elegans. Podbilewicz comments that Martin Chalfie, the 2008 Nobel Prize in Chemistry laureate, had previously shown that when a worm is hit on the body, it responds by moving away, demonstrating that the PVDs are necessary for
C. elegans to sense pain.
“The PVDs give rise to neuronal trees comprising structural units that we call ‘menorahs,’ because they look like Jewish candelabra,” says Podbilewicz, adding that each of these tiny branches is just one-millionth of an inch (or 30 nanometers) in diameter.
(l-r) In the lab at the Technion Faculty of Biology,
Using light to image and electron microscopy in both living specimens and dead
C. elegans, the team also studied how the number, structure, and function of these menorahs were maintained. In doing so, they discovered that a membrane protein called EFF-1 (which is also essential for the mediation of fusion between cells to form giant, multi-nucleate cells) has important roles in menorah formation and maintenance.
Prof. Benjamin Podbilewicz and his PhD student
According to Podbilewicz, EFF-1 also acts in the PVDs to trim the branches of neuronal tree menorahs. When the gene encoding for EFF-1 was deleted,
C. elegans displayed disorganized menorahs with many more branches; conversely, too much EFF-1 in the PVD reduced branching. By cutting, retracting, and fusing branches, EFF-1 prunes excess or abnormal branches, serving as part of a quality control process that is important for sculpting and maintenance of complicated menorahs.
C. elegans has just 302 neurons in comparison to the more than 100 billion neurons which humans are believed to possess. “The system we found in
C. elegans is ideal to use as a model to study pattern formation of more complicated neurons,” explains Oren-Suissa, “given the simplicity of
C. elegans and the amazingly stereotypic pattern of the ‘menorahs.’ In addition, we found that EFF-1 can lead to fusion within neurons - what we call ‘auto-fusion.’ This could potentially be used to repair damage caused to the nervous system following injury, or in neurodegenerative diseases,” she says.
Also contributing to this research were Dr Gidi Shemer of Technion; David Hall from the Albert Einstein College of Medicine; and Millet Treinin from the Hebrew University-Hadassah Medical School.