Heterogeneous Requirement of NGF for Sympathetic Target InnervationIn Vivo

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Abstract
The neurotrophin nerve growth factor (NGF) plays a crucial role in the development of the sympathetic nervous system. In addition to being required for sympathetic neuron survivalin vivoandin vitro, NGF has been shown to mediate axon growthin vitro. The role of NGF in sympathetic axon growthin vivo, however, is not clear because of its requirement for survival. This requirement can be circumvented by a concomitant deletion ofBax, a pro-apoptotic Bcl-2 family member, thus allowing an examination of the role of neurotrophins in axon growth independently of their function in cell survival. Here, we analyzed peripheral sympathetic target organ innervation in mice deficient for bothNGFandBax. In neonatalNGF-/-; Bax-/-mice, sympathetic target innervation was absent in certain organs (such as salivary glands), greatly reduced in others (such as heart), somewhat diminished in a few (such as stomach and kidneys), but not significantly different from control in some (such as trachea). At embryonic day 16.5, peripheral target sympathetic innervation was also reducedin NGF-/-; Bax-/-mice, with analogous variability for different organs. Interestingly, in some organs such as the spleen the precise location at which sympathetic axons become NGF-dependent for growth was evident. We thus show that NGF is required for complete peripheral innervation of both paravertebral and prevertebral sympathetic ganglia targetsin vivoindependently of its requirement for cell survival. Remarkably, target organs vary widely in their individual NGF requirements for sympathetic innervation.