Heterogeneous requirement of NGF for sympathetic target innervation in vivo

NO Glebova, DD Ginty - Journal of Neuroscience, 2004 - Soc Neuroscience
NO Glebova, DD Ginty
Journal of Neuroscience, 2004Soc Neuroscience
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 survival in
vivo and in vitro, NGF has been shown to mediate axon growth in vitro. The role of NGF in
sympathetic axon growth in vivo, however, is not clear because of its requirement for
survival. This requirement can be circumvented by a concomitant deletion of Bax, a pro-
apoptotic Bcl-2 family member, thus allowing an examination of the role of neurotrophins in …
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 survival in vivo and in vitro, NGF has been shown to mediate axon growth in vitro. The role of NGF in sympathetic axon growth in vivo, however, is not clear because of its requirement for survival. This requirement can be circumvented by a concomitant deletion of Bax, 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 both NGF and Bax. In neonatal NGF-/-; 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 reduced in 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 targets in vivo independently of its requirement for cell survival. Remarkably, target organs vary widely in their individual NGF requirements for sympathetic innervation.
Soc Neuroscience