Coordination of trophic interactions by separate developmental programs in sensory neurons and their target fields

In the developing vertebrate nervous system the survival of sensory neurons becomes dependent on neurotrophic factors when their axons reach their target fields, and the synthesis of nerve growth factor (NGF) by target field cells commences with the arrival of the earliest axons. The timing of NGF synthesis and the onset of neurotrophic factor dependence are not, however, reliant on innervation. NGF synthesis occurs on time in developing target fields in which innervation is prevented, and sensory neurons cultured before innervating their targets become dependent on neurotrophic factors for survival after a certain length of time in culture. The length of time neurons survive in culture before becoming neurotrophic factor-dependent is related to the time they would normally contact their targets in vivo: populations of neurons that have nearby targets which are innervated early respond to neurotrophic factors before neurons that have more distant targets which are innervated later. The timing of target field innervation is governed not only by the distance axons have to grow but by the rate at which they grow. Axonal growth rate is also regulated in accordance with target distance: neurons with distant targets extend axons faster than neurons with nearby targets. In addition to reviewing evidence for separate developmental programs that control the timing of neurotrophic factor synthesis in the target field and the onset of neurotrophic factor dependence in early sensory neurons, we will consider the mechanisms that might play a role in regulating the survival of neurons during the phase of neurotrophic factor independence.