Localized regulation of the axon shaft during the emergence of collateral branches.

Abstract

The ability of the axon to form de novo collateral branches along its length is fundamental to the establishment of complex patterns of connectivity during development and is also a major response of many axonal populations following injury. The emergence of branches is under both positive and negative control by extracellular signals. How the site of branch formation is determined is a fundamental question regarding the formation of branches. In theory, the whole axon shaft has the potential to give rise to a branch, but yet branches form only at specific sites. This feature of the formation of branches is emphasized by studies in which nerve growth factor (NGF), covalently attached to 10 micron beads, was applied locally along embryonic sensory axons (Gallo and Letourneau, 1998). Although contact of the beads with the axon shaft was able to drive the formation of a branch at the sites of contact, even after 3 hours of continuous contact only 46% of sites gave rise to a branch. Similarly, when NGF is bath applied to cultured sensory neurons, and thus the whole surface of the axon is exposed to NGF, axons usually only generate a maximum of 4–6 branches along the distal 100 microns of the axon, a response that is maximal by 30 minutes of treatment. Recent work, from our laboratory and others, has begun to shed light on why axons form branches at specific sites.