During normal embryonic development, a flat sheet of cells that is destined to give rise to the brain and spinal cord thickens and forms a groove with raised sides. Eventually, the sides of the groove fuse, almost like zipping a zipper, to form a hollow structure called the neural tube. If the neural tube does not "zip up" completely, it causes the brain and spinal cord to develop abnormally, resulting in defects that that range in severity from partial paralysis to death. These neural tube defects are relatively common, representing serious problems for 1/1000 live human births.

Details about what drives formation of the neural tube have remained elusive. But now, a study led by Drs. Eric Camerer and Shaun R. Coughlin from the Cardiovascular Research Institute at the University of California, San Francisco has shown that proteins called protease-activated receptors (PARs), which are best known for their role in tissue response to injury in adults, are required for neural tube closure. The researchers found that mice lacking specific PARs exhibited neural tube defects.

Interestingly, specific PARs and the protein that controls them were only active along the edges of the groove where and when the edges of the neural tube fused. These observations led the researchers to hypothesize that this PAR signaling system might sense the integrity of the tissue, as it does in the case of injuries, to regulate the closure of the tube. "Our discovery of molecular events that contribute to neural tube closure in mice might lead to insights into the complex mechanisms underlying human neural tube defects," concludes Dr. Coughlin.

The researchers include Eric Camerer, University of California, San Francisco, San Francisco, CA, INSERM, Paris Cardiovascular Research Center, Paris, France; Adrian Barker, University of California, San Francisco, San Francisco, CA; Daniel N. Duong, University of California, San Francisco, San Francisco, CA; Rajkumar Ganesan, Genentech, Inc., South San Francisco, CA; Hiroshi Kataoka, University of California, San Francisco, San Francisco, CA; Ivo Cornelissen, University of California, San Francisco, San Francisco, CA; Molly R. Darragh, University of California, San Francisco, San Francisco, CA; Arif Hussain, University of California, San Francisco, San Francisco, CA; Yao-Wu Zheng, University of California, San Francisco, San Francisco, CA; Yoga Srinivasan, University of California, San Francisco, San Francisco, CA; Christopher Brown, University of California, San Francisco, San Francisco, CA; Shan-Mei Xu, University of California, San Francisco, San Francisco, CA; Jean B. Regard, University of California, San Francisco, San Francisco, CA; Chen-Yong Lin, University of Maryland, Baltimore, MD; Charles S. Craik, University of California, San Francisco, San Francisco, CA; Daniel Kirchhofer, Genentech, Inc., South San Francisco, CA; and Shaun R. Coughlin, University of California, San Francisco, San Francisco, CA.

Note: If no author is given, the source is cited instead.

• Birth Defects
• Bone and Spine
• Nervous System

• Neuroscience
• Perception
• Brain Injury

• Central nervous system
• Spina bifida
• Neural development
• Placenta
• Neurobiology
• Umbilical cord