title: Visualization of Sensory Neurons and Their Projections in an Upper Motor Neuron Reporter Line.
abstract: Visualization of peripheral nervous system axons and cell bodies is important to understand their development, target recognition, and integration into complex circuitries. Numerous studies have used protein gene product (PGP) 9.5 [a.k.a. ubiquitin carboxy-terminal hydrolase L1 (UCHL1)] expression as a marker to label sensory neurons and their axons. Enhanced green fluorescent protein (eGFP) expression, under the control of UCHL1 promoter, is stable and long lasting in the UCHL1-eGFP reporter line. In addition to the genetic labeling of corticospinal motor neurons in the motor cortex and degeneration-resistant spinal motor neurons in the spinal cord, here we report that neurons of the peripheral nervous system are also fluorescently labeled in the UCHL1-eGFP reporter line. eGFP expression is turned on at embryonic ages and lasts through adulthood, allowing detailed studies of cell bodies, axons and target innervation patterns of all sensory neurons in vivo. In addition, visualization of both the sensory and the motor neurons in the same animal offers many advantages. In this report, we used UCHL1-eGFP reporter line in two different disease paradigms: diabetes and motor neuron disease. eGFP expression in sensory axons helped determine changes in epidermal nerve fiber density in a high-fat diet induced diabetes model. Our findings corroborate previous studies, and suggest that more than five months is required for significant skin denervation. Crossing UCHL1-eGFP with hSOD1G93A mice generated hSOD1G93A-UeGFP reporter line of amyotrophic lateral sclerosis, and revealed sensory nervous system defects, especially towards disease end-stage. Our studies not only emphasize the complexity of the disease in ALS, but also reveal that UCHL1-eGFP reporter line would be a valuable tool to visualize and study various aspects of sensory nervous system development and degeneration in the context of numerous diseases.
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Barış
authors.initials: B
authors.lastname: Genç
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Amiko Krisa Bunag
authors.initials: AK
authors.lastname: Lagrimas
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Pınar
authors.initials: P
authors.lastname: Kuru
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Hess
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Michael William
authors.initials: MW
authors.lastname: Tu
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Daniela Maria
authors.initials: DM
authors.lastname: Menichella
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Miller
authors.affiliation: Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America; Departments of Dermatology and Pediatrics, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America; Skin Disease Research Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America; Center for Genetic Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Paller
authors.affiliation: Davee Department of Neurology and Clinical Neurological Sciences, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America; Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States of America; Cognitive Neurology and Alzheimer's Disease Center, Northwestern University, Chicago, IL, United States of America.
authors.forename: P Hande
authors.initials: PH
authors.lastname: Özdinler
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D058948:Cell Tracking / Q000379:methods*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000235:genetics; D000072105:Superoxide Dismutase-1; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C000606290:SOD1 protein, human; C482860:UCHL1 protein, human; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C109415:SOD1 G93A protein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D043222:Ubiquitin Thiolesterase