ACTION OF A DIFFUSIBLE TARGET-DERIVED CHEMOATTRACTANT ON CORTICAL AXON BRANCH INDUCTION AND DIRECTED GROWTH

Cortical axons innervate their brainstem target, the basilar pens, by the initiation and extension of collateral branches interstitially along their length. To address whether a diffusible pens-derived chemoattractant controls these events, we used cocultures in collagen matrices and time-lapse microscopy. Pontine explants enhanced by 5-fold the de novo initiation of transient branches along cortical axons; most branches were directed toward pens. Of the branches extended toward pens, 2%-3% were stabilized; those extended away were not. Pontine explants also enhanced the stable bifurcation of growth cones and prompted directional changes by growth cone turning and collateral extension. These effects were distance dependent and mimicked by pens-conditioned medium. This evidence indicates that the pens activity promotes branch initiation interstitially along cortical axons, a novel property for a chemoattractant, and provides a directional cue for their growth. These findings suggest that the pens chemoattractant serves as a diffusible target-recognition molecule.