Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system
- PMID: 8126547
- PMCID: PMC6577586
- DOI: 10.1523/JNEUROSCI.14-03-01422.1994
Overexpression of nerve growth factor in epidermis of transgenic mice causes hypertrophy of the peripheral nervous system
Abstract
Survival of developing neurons is dependent on access to a limited supply of target-derived neurotrophic factors. NGF is the most extensively characterized of these molecules and during development is synthesized by neuronal and nonneuronal target tissues such as the skin. To investigate how target-derived NGF affects neuron survival and development of the PNS, we used an epidermal-specific gene promoter to produce transgenic mice that overexpress the mouse NGF cDNA in skin. Analysis of transgenic skin mRNA synthesis by Northern and in situ hybridizations showed increased levels of transgene-derived mRNA in the epidermis and associated hair follicles. The increase in NGF mRNA correlated with a hypertrophy of peripheral sensory and sympathetic nerves. Immunological analysis of skin using an anti-150 kDa neurofilament antibody showed numerous large nerve bundles and fibers coursing throughout the dermis. Increased numbers of nerve processes in the transgenic skin had immunoreactivity for calcitonin gene-related peptide and tyrosine hydroxylase, indicating that both the sensory and sympathetic systems were hypertrophied. The trigeminal and superior cervical ganglia were greatly enlarged. Cell counts of trigeminal ganglia of control and transgenic mice showed a 26-117% increase in the number of neurons in the transgenics, indicating a reduction or total prevention of the program of naturally occurring cell death. These results demonstrate that NGF production by the epidermal target tissue controls neuronal survival, and in so doing, establishes the level of innervation.
Similar articles
-
Cutaneous overexpression of NT-3 increases sensory and sympathetic neuron number and enhances touch dome and hair follicle innervation.J Cell Biol. 1996 Jul;134(2):487-97. doi: 10.1083/jcb.134.2.487. J Cell Biol. 1996. PMID: 8707832 Free PMC article.
-
Selective regulation of nerve growth factor expression in developing cutaneous tissue by early sensory innervation.Neural Dev. 2011 Apr 30;6:18. doi: 10.1186/1749-8104-6-18. Neural Dev. 2011. PMID: 21529369 Free PMC article.
-
Overexpression of nerve growth factor in skin causes preferential increases among innervation to specific sensory targets.J Comp Neurol. 1997 Nov 3;387(4):489-506. doi: 10.1002/(sici)1096-9861(19971103)387:43.0.co;2-z. J Comp Neurol. 1997. PMID: 9373009
-
Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia.Cell Tissue Res. 2009 Jun;336(3):349-84. doi: 10.1007/s00441-009-0784-z. Epub 2009 Apr 23. Cell Tissue Res. 2009. PMID: 19387688 Review.
-
NGF synthesis and NGF receptor expression in the embryonic mouse trigeminal system.J Physiol (Paris). 1990;84(1):100-3. J Physiol (Paris). 1990. PMID: 2162955 Review.
Cited by
-
Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve.Mol Pain. 2012 Jan 10;8:1. doi: 10.1186/1744-8069-8-1. Mol Pain. 2012. PMID: 22233577 Free PMC article.
-
Inositol 1,4,5-Trisphosphate Receptor Type 3 Regulates Neuronal Growth Cone Sensitivity to Guidance Signals.iScience. 2020 Mar 27;23(3):100963. doi: 10.1016/j.isci.2020.100963. Epub 2020 Mar 5. iScience. 2020. PMID: 32199289 Free PMC article.
-
Preserve and protect: maintaining axons within functional circuits.Trends Neurosci. 2014 Oct;37(10):572-82. doi: 10.1016/j.tins.2014.07.007. Epub 2014 Aug 26. Trends Neurosci. 2014. PMID: 25167775 Free PMC article. Review.
-
Link N as a therapeutic agent for discogenic pain.JOR Spine. 2018 Mar 15;1(1):e1008. doi: 10.1002/jsp2.1008. eCollection 2018 Mar. JOR Spine. 2018. PMID: 31463438 Free PMC article.
-
Responses of mature and aged sympathetic neurons to laminin and NGF: an in vitro study.Neurochem Res. 1997 Aug;22(8):1003-11. doi: 10.1023/a:1022478926949. Neurochem Res. 1997. PMID: 9239756
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases