DUAL-ACTION OF A LIGAND FOR EPH RECEPTOR TYROSINE KINASES ON SPECIFICPOPULATIONS OF AXONS DURING THE DEVELOPMENT OF CORTICAL CIRCUITS

The structural basis of cortical columns are radially oriented axon co llaterals that form precise connections between distinct cortical laye rs. During development, these connections are highly specified from th e initial outgrowth of collateral branches. Our previous work provided evidence for positional cues confined to individual layers that induc e and/or prevent the formation of axon collaterals in specific populat ions of cortical neurons. Here we demonstrated with in situ hybridizat ion techniques that mRNA of the Eph receptor tyrosine kinase EphA5 and one of its ligands, ephrin-A5, are present in distinct cortical layer s, 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 expr essing ephrin-A5, In contrast to its established role as a repulsive a xonal guidance signal, ephrin-A5 specifically mediates sprouting of th ose 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 po pulations of axons suggest that ephrin-A5 plays a role in the assembly of local cortical circuits.