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Date:12/28/2009

Spinal cord disorders like spina bifida arise during early development when future spinal cord cells growing in a flat layer fail to roll up into a tube. In the Dec. 6 issue of Nature Cell Biology, researchers from the Johns Hopkins University School of Medicine team with colleagues at the University of California, Berkeley to report a never-before known link between protein transport and mouse spinal cord development, a discovery that opens new doors for research on all spinal defects.

"What I love about this discovery is the total surprise we never before would have linked defects in the protein-secretion machinery and neural tube closure," says David Ginty, Ph.D., professor of neuroscience and Howard Hughes Medical Institute investigator.

The team originally set out to find new genes that instruct proper wiring of the hundred billion neurons in the nervous system. To do that, they randomly generated mutations in mouse genes, bred the mice and examined offspring for defects in nervous system development. One of the thousands of mouse embryos examined by graduate student Janna Merte had a spinal cord that had failed to close into a tube. Whereas conditions like spina bifida arise from failure of the tail end of the spinal cord to close, these new mice had a more severe condition, where the entire length of the spinal tube had failed to close.

Intrigued, Janna then identified the mutated gene in this mouse as Sec24b, a gene already known to play a role in the process where cells package newly made proteins that are destined to be delivered to the cell membrane or sent to the outside of the cell. But all genes known to instruct normal spinal tube closure are known to orient cells in a flat sheet, similar to patterning of the hair follicles in skin.

"We didn't really know what to do with Sec24b at first," says Ginty. His team consulted and eventually teamed up with Berkeley professor Randy Schekman, who discovered the
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Contact: Audrey Huang
audrey@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
Source:Eurekalert

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