Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice

Laurie C. Eldredge, Xiaoguang M. Gao, David H. Quach, Lin Li, Xiaoqiang Han, Jon Lomasney, Warren G. Tourtellotte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Sympathetic nervous system development depends upon many factors that mediate neuron migration, differentiation and survival. Target tissue-derived nerve growth factor (NGF) signal ing-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.

Original languageEnglish (US)
Pages (from-to)2949-2957
Number of pages9
JournalDevelopment
Volume135
Issue number17
DOIs
StatePublished - Sep 2008

Keywords

  • Egr3
  • Mouse
  • Neurotrophin
  • Physiology
  • Ptosis
  • Sympathetic

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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