Earliest sensory nerve fibres are guided to peripheral targets by attractants other than nerve growth factor

Recent studies have shown that developing nerve fibres grow directly to their targets and are guided by specific cues, but the nature of these cues and the mechanism of guidance remain unknown. The growth of sympathetic axons towards an artificial source of nerve growth factor (NGF) in vivo and of sensory neurites up a concentration gradient of NGF in vitro has supported the hypothesis that NGF, produced by target tissues, acts as a chemotactic attractant for these nerve fibres during development. Both these studies and those of the influence of NGF or target tissues on neurite growth in vitro were conducted late in development when, following target encounter, the neurones had become dependent on NGF or target for survival. Here we have co-cultured embryonic mouse sensory neurones and their peripheral target tissue at a stage preceding their contact in vivo. Neurites grew directly and exclusively towards their own target but not to regionally inappropriate peripheral tissue. Antiserum to isogeneric NGF did not reduce this outgrowth but did reduce undirected neurite outgrowth which occurred in co-cultures of older neurones with denervated target tissue. These results demonstrate that agents other than NGF guide neurites of NGF-responsive neurones in development.