Target Control of Collateral Extension and Directional Axon Growth in the Mammalian Brain

TLDR

Axon targeting mechanisms remain unclear, but the mammalian corticopontine projection offers a tractable system to study axon outgrowth, branching, and target selection. Corticospinal axons that have passed the pons generate delayed interstitial collateral buds that grow into the basilar pons, and in 3‑D collagen cocultures the basilar pons induces directional collateral growth. The basilar pons releases a diffusible chemotropic molecule that selectively attracts collaterals from appropriate cortical layers, demonstrating target‑specific control of collateral extension.

Abstract

Individual neurons in the brain send their axons over considerable distances to multiple targets, but the mechanisms governing this process are unresolved. An amenable system for studying axon outgrowth, branching, and target selection is the mammalian corticopontine projection. This major connection develops from parent corticospinal axons that have already grown past the pons, by a delayed interstitial budding of collateral branches that then grow directly into their target, the basilar pons. When cocultured with explants of developing cortex in three-dimensional collagen matrices, the basilar pons elicits the formation and directional growth of cortical axon collaterals across the intervening matrix. This effect appears to be target-specific and selectively influences neurons in the appropriate cortical layer. These in vitro findings provide evidence that the basilar pons becomes innervated by controlling at a distance the budding and directed ingrowth of cortical axon collaterals through the release of a diffusible, chemotropic molecule.