The concept of uptake and retrograde transport of neurotrophic molecules during development: history and present status.

In the present review honoring Hans Thoenen's contributions to the concept of uptake and retrograde transport of trophic molecules, I have attempted to identify the major historical pathways that had to converge before this concept could be accepted as a fundamental principle in neurobiology. Some of the critical events in this history which are discussed here include: neuron-target interactions, bidirectional trophic signals, axoplasmic transport, receptor-mediated endocytosis, transneuronal trophic signals, the discovery of NGF, the retrograde transport of NGF, and the production of NGF by target tissues. Only when all of these diverse pieces of the puzzle were in place was the concept finally confirmed as being the mechanism that mediates the many phenomena attributed to the regulation and maintenance of neurons by their targets.