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The Journal of Neuroscience, June 15, 1998, 18(12):4663-4672
Dual Action of a Ligand for Eph Receptor Tyrosine Kinases on Specific Populations of Axons during the Development of Cortical Circuits
Valérie Castellani1, Yong Yue2, Pan-Pan Gao2, Renping Zhou2, and Jürgen Bolz1 1 Institut National de la Santé et de la Recherche Médicale Unité 371 "Cerveau et Vision," 69500 Bron, France, and 2 Laboratory for Cancer Research, Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855
The structural basis of cortical columns are radially oriented axon collaterals that form precise connections between distinct cortical layers. During development, these connections are highly specified from the initial outgrowth of collateral branches. Our previous work provided evidence for positional cues confined to individual layers that induce and/or prevent the formation of axon collaterals in specific populations of cortical neurons. Here we demonstrated with in situ hybridization techniques that mRNA of the Eph receptor tyrosine kinase EphA5 and one of its ligands, ephrin-A5, are present in distinct cortical layers, at a time when intrinsic connections are being formed in the cortex. Axonal guidance assays indicate that ephrin-A5 is a repellent signal for a populations of axons that in vivo avoid the cortical layer expressing ephrin-A5. In contrast to its established role as a repulsive axonal guidance signal, ephrin-A5 specifically mediates sprouting of those cortical axons that target the ephrin-A5-expressing layer in vivo. These results identify a novel function of ephrin-A5 on axonal arbor formation. The laminar distribution and the dual action on specific populations of axons suggest that ephrin-A5 plays a role in the assembly of local cortical circuits.
Key words: wiring molecules; cortical development; cortical circuit formation; axonal guidance; axonal branching; ephrins; Eph receptors; in vitro assays
Copyright © 1998 Society for Neuroscience 0270-6474/98/18124663-10$05.00/0
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