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The Journal of Neuroscience, January 1, 2003, 23(1):193-202

Gradient Steepness Influences the Pathfinding Decisions of Neuronal Growth Cones In Vivo

Carolyn M. Isbister^{1, 3}, Paul J. Mackenzie³, Kenneth C. W. To³, and Timothy P. O'Connor^{1, 2, 3}

Departments of ¹ Anatomy and ² Zoology and ³ Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3

Gradients of chemotropic molecules are generally thought to be fundamental for the guidance of neuronal growth cones in the developing embryo. Here we show that the grasshopper-secreted semaphorin Sema 2a is expressed in a gradient during the period of tibial Ti1 pioneer axon pathfinding into the CNS. At two critical Ti1 growth cone choice points, the Sema 2a gradient differs in steepness, whereas the absolute concentration is the same. Although Ti1 growth cones enter and extend up both steep and shallow gradients of Sema 2a, fewer projection errors occur along the steep gradient, suggesting that the steepness of the gradient encodes the critical guidance information into the pathfinding growth cone. In contrast, an increase in the absolute concentration of Sema 2a appears to constrain the Ti1 growth cone size. Using these in vivo gradients, we provide evidence that the Ti1 growth cone detects the Sema 2a gradient by measuring the fractional change in Sema 2a concentration, thereby demonstrating one mechanism that neuronal growth cones may use to detect and read gradients in vivo.

Key words: gradient; axonal guidance; growth cone; semaphorins; chemorepulsion; grasshopper

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Copyright © 2003 Society for Neuroscience  0270-6474/03/231193-10$05.00/0

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