Yimin Zou, Ph.D., Assistant Professor in the Department of Neurobiology, Pharmacology, and Physiology, and colleagues have made a major discovery in the field of developmental neurobiology. These results were published as “Anterior-Posterior Guidance of Commissural Axons by Wnt-Frizzled Signaling” in the December 12, 2003, issue of Science.

The Zou lab concentrates on the molecular mechanisms governing axon guidance in vertebrate development. The vertebrate nervous system is wired along the dorsoventral and anteroposterior body axes. Although relatively more is known about the dorsal-ventral patterning of axons, very little is known about the mechanisms of anterior-posterior axon patterning. This lack of knowledge is particularly unfortunate, given the fact that the anterior-posterior axons are essential for spinal cord communication with the brain. Sensory signals related to pain and temperature, for example, ascend from the spinal cord to the brain while motor commands descend from the brain to the spinal cord.

In order to study anterior-posterior axon guidance, Zou established a primary model system focusing on commisural axons, which cross the midline at the floor plate of developing spinal cord. After crossing the midline, these axons turn immediately rostrally along the entire anteroposterior axis, ultimately finding their way to the brain. The question Zou sought to answer is a longstanding mystery in neurodevelopment: what molecular cue(s) are responsible for this directional patterning?

Using a series of elegant assays, his lab found that it is a continuous molecular gradient inside the spinal cord that controls guidance along the anterior-posterior axis. Several Wnt proteins are responsible for stimulating the extension of post-crossing but not pre-crossing commissural axons. It is the Wnt4 protein, in fact, that likely plays the primary instructive role.

Zou’s findings will likely pioneer a new field in axon guidance. They also have very clear implications for the field of spinal cord injury. Because damaged spinal cord axons cannot regenerate normally, in order to promote regeneration, scientists must gain a complete understanding of the basic molecular events controlling axon guidance. Zou’s results are a critical first step on the way.

The co-authors of the paper are first-author Anna Lyuksyutova, along with Chin-Chun Lu, Nancy Milanesio, and Leslie King from the University of Chicago; Nino Guo, Yanshu Wang, and Jeremy Nathans from Johns Hopkins University; and Marc Tessier-Lavigne from Stanford University.

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A research team led by Rima McLeod, M.D., Professor of Ophthalmology and Visual Sciences, has discovered a method of delivering antimicrobial drugs to infectious parasites that cause diseases such as toxoplasmosis. The method, published in the November 17-21 issue of the Proceedings of the National Academy of Sciences, allows the antimicrobials to target hidden and inactive parasites within cysts, where conventional medications can’t reach them. “This is a major step forward in developing ways to treat one of mankind’s most common chronic infections,” said McLeod. “For the first time, we have access to this microbe in its latent stage, a part of its life cycle that was previously inaccessible.”

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