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Chemical Signaling Helps Regulate Sensory Map Formation In The Brain

olleagues reveal a new role for Wnts. They show that a gradient of Wnt3 along the medial-lateral axis within the developing brain is the opposing regulating force, working along with ephrinB1 to specify the topographic target selection in the optic tectum, a brain region that processes information from the eye.

At the molecular-signaling level, Wnt3 acts through two different classes of growth-cone receptors, Ryk and the Frizzled(s), to pattern topographic connections in the brain. Disrupting either the Wnt or ephrin pathway throws the growing axons off their targets, shifting the map from side to side.

This counterbalancing force has two components, Zou's team discovered, with one receptor drawn toward certain concentrations of Wnt3 and the other driven away. "A repulsive Wnt-Ryk pathway competes with an attractive Wnt-Frizzled interaction," the authors write, "to titrate the response to Wnt3 protein at different concentrations." The net outcome of the competition, they conclude, "determines the topographic connections by providing a lateral directed mapping force."

The research was supported by the National Institutes of Health, the Alfred Sloan Foundation, and the Schweppe Foundation. Additional authors of the study include Adam Schmitt, Jun Shi, Alex Wolf, Chin-Chun Lu and Leslie King at the University of Chicago.
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