Genes and Nerves

roundworm’s PVD neuron shows normal branching of its dendrites
A: This color-enhanced image of the roundworm’s PVD neuron shows normal branching of its dendrites. The branches resemble menorahs—hence the name mnr-1 for the newly identified gene that orchestrates the process. B: Mutation of the mnr-1 gene has resulted in defective PVD dendrite branching. Courtesy of Cell and Yehuda Salzberg, Ph.D.

Our ability to detect heat, touch, tickling and other sensations depends on our sensory nerves. Now, for the first time, Einstein researchers have identified a gene that orchestrates the crucially important branching of nerve fibers that occurs during development. This gene belongs to an entire class of genes that had no known function in any organism. The findings were published last October in the journal Cell. The research focuses on dendrites, the stringlike extensions of sensory nerves that penetrate tissues of the skin, eyes and other sensory organs. “The formation of dendritic branches—‘arbors’ as we call them—is vital for allowing sensory nerves to collect information and sample the environment appropriately,” says Hannes E. Buelow, Ph.D., senior author of the Cell paper and an associate professor of genetics at Einstein. “These arbors vary greatly in shape and complexity, reflecting the different types of sensory input they receive. The loss of dendritic complexity has been linked to a range of neurological problems, including Alzheimer’s disease, schizophrenia and autism spectrum disorders.” Dr. Buelow is also an associate professor in the Dominick P. Purpura Department of Neuroscience.

Scanning electron micrograph of tail region of adult male roundworm. Photo by Carolyn Marks and David Hall, Einstein department of neuroscience

The Einstein scientists were looking for genes that organize the structure of the developing nervous system. They focused on a pair of roundworm sensory neurons, known as PVD neurons, which together produce the largest web of dendrites of any neurons in the roundworm—a sensory web that covers almost the entire skin surface of the worm and detects pain and extreme temperatures. Suspecting that a gene acts in the skin to “instruct” nearby dendrites to branch, the researchers set out to identify the one responsible.

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The dendritic branches of PVD neurons had previously been described as resembling menorahs, so the Einstein scientists named the newly identified gene mnr-1. The mnr1 gene’s newly identified function in orchestrating dendrite branching is presumably not limited to roundworms. Versions of this gene are present in multicellular animals from the simplest to the most complex, including humans. Genes conserved in this way, through millions of years of evolution, tend to be genes that are absolutely necessary for maintaining life.

The paper’s lead author was Yehuda Salzberg, Ph.D., a postdoctoral fellow in Dr. Buelow’s lab.