Fig. 7. Schematic representation of the sympathetic neurons in wild type and in the different CREB mutants. Survival of developing neurons depends on availability of NGF produced by target organs (black dots). Neurons not receiving enough neurotrophin undergo apoptotic cell death (broken line). Black and white nuclei indicate the presence or absence of CREB. In Creb^-/- mutants CREB expression is lost in the developing neurons and also in the target cells, where CREB may be required to express molecular cues prior to neurotrophin dependence. Loss of CREB in sympathetic neurons and target cells results in partial misplacement of the neurons and in increased neuronal death, possibly exacerbated by the reduced neurotrophic supply. In the conditional mutants, CREB expression is lost only in noradrenergic neurons of sympathetic ganglia, resulting in an increased number of surviving neurons. The neurotrophic supply from target organs is probably unaffected. This scenario indicates cell autonomous pro-survival mechanisms operative in the absence of CREB.