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Scientists Crack Code for Motor Neuron Wiring
by Paul Muhlrad
As you turn the pages of this Bulletin, motor neurons that project from your spinal cord are coordinating the precise actions of more than 50 muscles in each of your arms. Each muscle is individually controlled by its own motor neuron cluster, which has a distinct identity and pattern of connectivity. "Motor neurons represent an extreme example of neuronal diversification," says HHMI investigator Thomas M. Jessell, whose research group at Columbia University Medical Center is seeking to understand how a developing embryo delegates specialized functions to different nerve cells.
"Its first task is to make motor neurons, as a class, different from all the other classes of neurons," says Jessell. "And once the embryo has solved that problem it has to generate distinct columns of motor neurons in the spinal cord, with each column controlling a particular body region, such as a limb. Then, within each column, the embryo has to generate motor neuron pools, each of which activates one particular muscle." Motor axons must then grow from the spinal cord into the limbs and elsewhere and target the right muscle.
Jessell's team recently deciphered the code that assigns unique identities to the motor neuron pools. This code, as the researchers explained in the November 4, 2005, issue of Cell, is written in the language of Hox proteins—a family of transcription factors (proteins that activate specific sets of genes) found in virtually all organisms.
Scientists have long recognized that Hox proteins, by orchestrating a cascade of gene expression in the early embryo, ensure animals' overall body plan. They place the head at the top, the feet below, and the correct arrangement of ribs in between.
Four years ago, the Columbia group discovered that Hox proteins also influence the arrangement of the motor neuron columns within the spinal cord. That finding prompted the recent study, in which Jeremy S. Dasen, an HHMI research associate in Jessell's lab, painted chick embryos with a palette of fluorescently tagged antibodies directed against many of the 39 Hox proteins. The experiments were painstaking and meticulous, says Jessell. Merely generating the antibodies was a 5-year effort by Bonnie C. Tice and Susan Brenner-Morton, Dasen's labmates and coauthors of the Cell paper.
The hard work paid off. What has emerged from these experiments is a detailed motor neuron atlas that shows the locations of relevant Hox proteins in the chick embryo at different times during development. The appearance and disappearance of the different protein types in distinct motor neuron pools revealed the molecular logic at work to Dasen and his colleagues. "Different Hox proteins have specific tasks that progressively determine motor neuron identity,' Jessell explains.