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Scientists crack code for motor neuron wiring

Howard Hughes Medical Institute (HHMI) researchers have deciphered a key part of the regulatory code that governs how motor neurons in the spinal cord connect to specific target muscles in the limbs.

The researchers said that understanding this code may help guide progress in restoring motor neuron function in people whose spinal cords have been damaged by trauma or disease. The studies suggest that the code -- which involves members of the family of transcription factors encoded by the Hox genes -- could also govern the establishment of other spinal cord circuits. This circuitry includes interneurons that control motor neuron firing patterns and sensory neurons that transmit feedback information on muscle action.

The research team, which was led by HHMI investigator Thomas M. Jessell, published its findings in the November 4, 2005, issue of the journal Cell. Jessell collaborated on the studies with HHMI research associate Jeremy S. Dasen, Bonnie C. Tice and Susan Brenner-Morton, all of whom are at Columbia University. The work was also funded by grants from the National Institute of Neurological Disorders and Stroke and Project ALS.

According to Jessell, members of the Hox gene family had been known to regulate aspects of brain development, but "few people had paid attention to the fact that these genes are also expressed in the spinal cord." Earlier work performed by Dasen and Jessell, in collaboration with Jeh-Ping Liu, who is now at the University of Virginia, established that certain Hox proteins control the differentiation of motor neurons into columns in the spinal cord. These columns, which are arrayed along the anterior-posterior length of the spinal cord, form in the initial phases of motor neuron organization. That organization determines whether motor neurons grow to the limbs or to other targets.

Creation of antibodies that react with each of the 21 Hox proteins expressed by spinal cord motor neurons was an important tech
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Source:Howard Hughes Medical Institute


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