title: A sympathetic neuron autonomous role for Egr3-mediated gene regulation in dendrite morphogenesis and target tissue innervation.
abstract: Egr3 is a nerve growth factor (NGF)-induced transcriptional regulator that is essential for normal sympathetic nervous system development. Mice lacking Egr3 in the germline have sympathetic target tissue innervation abnormalities and physiologic sympathetic dysfunction similar to humans with dysautonomia. However, since Egr3 is widely expressed and has pleiotropic function, it has not been clear whether it has a role within sympathetic neurons and if so, what target genes it regulates to facilitate target tissue innervation. Here, we show that Egr3 expression within sympathetic neurons is required for their normal innervation since isolated sympathetic neurons lacking Egr3 have neurite outgrowth abnormalities when treated with NGF and mice with sympathetic neuron-restricted Egr3 ablation have target tissue innervation abnormalities similar to mice lacking Egr3 in all tissues. Microarray analysis performed on sympathetic neurons identified many target genes deregulated in the absence of Egr3, with some of the most significantly deregulated genes having roles in axonogenesis, dendritogenesis, and axon guidance. Using a novel genetic technique to visualize axons and dendrites in a subpopulation of randomly labeled sympathetic neurons, we found that Egr3 has an essential role in regulating sympathetic neuron dendrite morphology and terminal axon branching, but not in regulating sympathetic axon guidance to their targets. Together, these results indicate that Egr3 has a sympathetic neuron autonomous role in sympathetic nervous system development that involves modulating downstream target genes affecting the outgrowth and branching of sympathetic neuron dendrites and axons.
authors: Department of Pathology (Division of Neuropathology), Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
authors: David H
authors: DH
authors: Quach
authors: Michelle
authors: M
authors: Oliveira-Fernandes
authors: Katherine A
authors: KA
authors: Gruner
authors: Warren G
authors: WG
authors: Tourtellotte
mesh_terms: D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000235:genetics / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D051776:Early Growth Response Protein 3 / Q000235:genetics; D018274:Electroporation; D005728:Ganglia, Sympathetic / Q000166:cytology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D049452:Green Fluorescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: C497369:Egr3 protein, mouse; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C485184:enhanced green fluorescent protein; D051776:Early Growth Response Protein 3; D049452:Green Fluorescent Proteins; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D001616:beta-Galactosidase