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Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice
- Source :
- Development (Cambridge, England). 135(17)
- Publication Year :
- 2008
-
Abstract
- Sympathetic nervous system development depends upon many factors that mediate neuron migration, differentiation and survival. Target tissue-derived nerve growth factor (NGF) signaling-induced gene expression is required for survival, differentiation and target tissue innervation of post-migratory sympathetic neurons. However, the transcriptional regulatory mechanisms mediated by NGF signaling are very poorly defined. Here, we identify Egr3, a member of the early growth response (Egr) family of transcriptional regulators, as having an important role in sympathetic nervous system development. Egr3 is regulated by NGF signaling and it is expressed in sympathetic neurons during development when they depend upon NGF for survival and target tissue innervation. Egr3-deficient mice have severe sympathetic target tissue innervation abnormalities and profound physiological dysautonomia. Unlike NGF, which is essential for sympathetic neuron survival and for axon branching within target tissues, Egr3 is required for normal terminal axon extension and branching, but not for neuron survival. The results indicate that Egr3 is a novel NGF signaling effector that regulates sympathetic neuron gene expression required for normal target tissue innervation and function. Egr3-deficient mice have a phenotype that is remarkably similar to humans with sympathetic nervous system disease, raising the possibility that it may have a role in some forms of human dysautonomia,most of which have no known cause.
- Subjects :
- medicine.medical_specialty
Sympathetic nervous system
Sympathetic Nervous System
Apoptosis
Arylalkylamine N-Acetyltransferase
Pineal Gland
Article
Mice
Cell Movement
Internal medicine
Ganglia, Spinal
Nerve Growth Factor
Deficient mouse
medicine
Animals
Blepharoptosis
Molecular Biology
Early Growth Response Protein 3
Regulation of gene expression
Neurons
biology
Axon extension
Dysautonomia
Gene Expression Regulation, Developmental
Heart
Axons
medicine.anatomical_structure
Endocrinology
Nerve growth factor
nervous system
Animals, Newborn
Autonomic Nervous System Diseases
biology.protein
Neuron
Signal transduction
medicine.symptom
Neuroscience
Developmental Biology
Neurotrophin
Signal Transduction
Subjects
Details
- ISSN :
- 09501991
- Volume :
- 135
- Issue :
- 17
- Database :
- OpenAIRE
- Journal :
- Development (Cambridge, England)
- Accession number :
- edsair.doi.dedup.....597e0011b179817729b07abc6671fa47