Extension of sympathetic neurites in vitro towards explants of embryonic and neonatal mouse heart and stomach: ontogeny of neuronotrophic factors.

In order to establish when target organs first produce neuronotrophic factors, extension of neurites in vitro from sympathetic ganglia (superior cervical and coeliac) of 1-day neonatal mice towards explants of 10-, 11-, 14- and 17-day embryonic and 1-day neonatal atrium and stomach was examined in co-cultures. Longer neurites extended from ganglia towards, than away from, atrial targets at all stages examined, and was most marked towards 17-day embryonic and neonatal explants. Treatment of atrial co-cultures with antiserum to nerve growth factor (NGF) almost totally blocked preferential neurite outgrowth. Directional growth of neurites towards stomach explants in co-cultures was not as pronounced as that towards atrium; extension of neurites was most marked when stomach was provided by 11-, 14- and 17-day embryos. Such outgrowth was only partially blocked by antiserum to NGF, significant preferential extension of neurites towards stomach persisting in the presence of the antiserum. These results indicate that atrium and stomach produce neuronotrophic factors from the earliest ages studied; the evidence indicates that in the case of atrium, NGF predominates but that stomach produces NGF as well as another factor immunologically distinct from NGF. It is of interest that both types of target explanted before they receive sympathetic innervation show evidence of producing NGF in culture.