Wnt5a Induces Simultaneous Cortical Axon Outgrowth and Repulsive Axon Guidance through Distinct Signaling Mechanisms

• DOI: 10.1523/jneurosci.0183-09.2009
• Publication Date: 2009-05-06T17:33:18Z
• Authors: Li Li; B. Ian Hutchins; Katherine Kalil
• Keywords: Boron Compounds; Cerebral Cortex; Neurons; Analysis of Variance; 0303 health sciences; Dose-Response Relationship, Drug; Mesocricetus; Green Fluorescent Proteins; Imidazoles; Calcium Channel Blockers; Axons; Frizzled Receptors; 03 medical and health sciences; Electroporation; Animals, Newborn; Cell Movement; Cricetinae; Animals; Calcium; Calcium Signaling; Estrenes; Cells, Cultured

Wnts are morphogens that also function as axon guidance molecules.In vivoWnt5a gradients via Ryk receptors were found to repel cortical axons into developing callosal and corticospinal pathways. Here, using dissociated cortical cultures, we found that bath-applied Wnt5a increased axon outgrowth. In turning assays, Wnt5a gradients simultaneously increased axon outgrowth and induced repulsive turning, a potential mechanism for propelling cortical axonsin vivo. We found that axon outgrowth is mediated by Ryk, whereas axon repulsion requires both Ryk and Frizzled receptors. Both receptors mediate Wnt-evoked fluctuations in intracellular calcium, which is required for increased axon outgrowth and repulsion by Wnt5a. However, whereas increased axon outgrowth involves calcium release from stores through IP3 receptors as well as calcium influx through TRP channels, axon repulsion is mediated by TRP channels without involvement of IP3 receptors. These results reveal distinct signaling mechanisms underlying Wnt5a-induced axon outgrowth and repulsive guidance.