title: Ephrin-A5 deficiency alters sensorimotor and monoaminergic development.
abstract: The Eph receptors and their ligands, the ephrins, play an important role during neural development. In particular, ephrin-A5 is highly expressed in the developing nervous system in several brain regions including the olfactory bulb, frontal cortex, striatum and hypothalamus. Although a number of studies have characterized the expression of ephrin-A5 in these regions, very little is known about the functional consequences that might follow alterations in the expression of this ligand. Previously, we demonstrated that ephrin-A5 acts as a guidance molecule regulating the trajectory of the ascending midbrain dopaminergic pathways. In light of this finding and the critical role of dopamine in modulating a number of behaviors, we sought to determine whether loss of ephrin-A5 altered neurobehavioral development. Our results indicate that ephrin-A5-null mice exhibit delays in reaching developmental milestones and in the maturation of motor skills. In addition, they exhibit increased locomotor activity and reduced levels of brain monoamines. Therefore, we conclude that ephrin-A5 expression appears to be critical for proper development of central monoaminergic pathways and that its loss results in a number of neurodevelopmental abnormalities. Because alterations in monoamine function are associated with a variety of neurodevelopmental disorders, these data suggest that further study on the potential role of ephrin-A5 in such disorders is warranted.
authors.affiliation: Departments of Chemical Biology, Susan Lehman-Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States.
authors.forename: Michal
authors.initials: M
authors.lastname: Sheleg
authors.affiliation: Environmental and Occupational Health Sciences Institute, a Joint Institute of Robert Wood Johnson Medical School and Rutgers University, Piscataway, NJ 08854, United States.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Yochum
authors.affiliation: Environmental and Occupational Health Sciences Institute, a Joint Institute of Robert Wood Johnson Medical School and Rutgers University, Piscataway, NJ 08854, United States; Department of Psychology, Rutgers University, New Brunswick, NJ 08854, United States.
authors.forename: George C
authors.initials: GC
authors.lastname: Wagner
authors.affiliation: Departments of Chemical Biology, Susan Lehman-Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, United States. Electronic address: michal.hausfater@gmail.com.
authors.forename: Renping
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Environmental and Occupational Health Sciences Institute, a Joint Institute of Robert Wood Johnson Medical School and Rutgers University, Piscataway, NJ 08854, United States. Electronic address: jricha3@eohsi.rutgers.edu.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Richardson
mesh_terms: D000375:Aging / Q000502:physiology / Q000523:psychology; D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D015306:Biogenic Monoamines / Q000502:physiology*; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D036386:Ephrin-A5 / Q000172:deficiency*; D005123:Eye / Q000254:growth & development; D005838:Genotype; D018737:Hand Strength / Q000502:physiology; D007398:Interpersonal Relations; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009046:Motor Neurons / Q000502:physiology*; D017072:Neostriatum / Q000254:growth & development / Q000378:metabolism; D009420:Nervous System / Q000254:growth & development*; D010988:Play and Playthings; D004856:Postural Balance / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D011984:Sensory Receptor Cells / Q000502:physiology*; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D050483:Dopamine Plasma Membrane Transport Proteins; D036386:Ephrin-A5; C493453:Slc18a2 protein, mouse; D050493:Vesicular Monoamine Transport Proteins