TrkA Expression Levels of Sympathetic Neurons Correlate with NGF-dependent Survival During Development and After Treatment with Retinoic Acid

Sympathetic neurons depend on the classical neurotrophin nerve growth factor (NGF) for survival by the time they innervate their targets, but not before. The acquisition of NGF responsiveness is thought to be controlled by environmental cues in sympathetic neurons. We have investigated the expression of the signal transducing NGF receptor trkA on mRNA and protein level during development of chick sympathetic neurons obtained from lumbosacral, paravertebral chain ganglia between embryonic days (E) 6.5 and 10. We demonstrate that trkA mRNA levels increase between E6.5 and E10, whereas the levels of trkC and p75 do not change. We also observed a similar increase in trkA protein during this time period. This increase correlates with the increase in NGF-dependent survival of sympathetic neurons from the corresponding stages in vitro. To define the correlation between trkA expression and NGF-mediated survival in more detail, trkA expression was adjusted to different levels by treatment with increasing concentrations of retinoic acid. We observed that small changes of trkA mRNA expression levels, below one order of magnitude, are decisive for the ability of immature sympathetic neurons to survive in the presence of NGF. A small and transient increase in trkA mRNA expression was also elicited in vivo by application of retinoids. These data provide evidence that sympathetic neurons upregulate the NGF receptor trkA and in this way acquire NGF-dependency.