egr3 dependent sympathetic target tissue innervation in the absence of neuron deathegr3依赖同情靶组织神经支配没有神经元的死亡.pdfVIP

Egr3 Dependent Sympathetic Target Tissue Innervation in the Absence of Neuron Death 1 1 1 1 1 Lin Li , Laurie C. Eldredge , David H. Quach , Avinash Honasoge , Katherine Gruner , Warren G. Tourtellotte1,2,3* 1 Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America, 2 Division of Neuropathology, Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America, 3 Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America Abstract Nerve Growth Factor (NGF) is a target tissue derived neurotrophin required for normal sympathetic neuron survival and target tissue innervation. NGF signaling regulates gene expression in sympathetic neurons, which in turn mediates critical aspects of neuron survival, axon extension and terminal axon branching during sympathetic nervous system (SNS) development. Egr3 is a transcription factor regulated by NGF signaling in sympathetic neurons that is essential for normal SNS development. Germline Egr3-deficient mice have physiologic dysautonomia characterized by apoptotic sympathetic neuron death and abnormal innervation to many target tissues. The extent to which sympathetic innervation abnormalities in the absence of Egr3 is caused by altered innervation or by neuron death during development is unknown. Using Bax- deficient mice to abrogate apoptotic sympathetic neuron death in vivo, we show that Egr3 has an essential role in target tissue innervation in the absence of neuron death. Sympathetic target tissue innervation is abnormal in many target tissues in the absence of neuron death, and like NGF, Egr3 also appear