Ephrin-A5 deficiency alters sensorimotor and monoaminergic development

Behav Brain Res. 2013 Jan 1;236(1):139-147. doi: 10.1016/j.bbr.2012.08.032. Epub 2012 Aug 27.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / physiology
  • Aging / psychology
  • Animals
  • Axons / physiology
  • Behavior, Animal / physiology
  • Biogenic Monoamines / physiology*
  • Blotting, Western
  • Body Weight / physiology
  • Brain Chemistry / physiology
  • Chromatography, High Pressure Liquid
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Ephrin-A5 / deficiency*
  • Eye / growth & development
  • Genotype
  • Hand Strength / physiology
  • Interpersonal Relations
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Motor Neurons / physiology*
  • Neostriatum / growth & development
  • Neostriatum / metabolism
  • Nervous System / growth & development*
  • Play and Playthings
  • Postural Balance / physiology
  • Real-Time Polymerase Chain Reaction
  • Sensory Receptor Cells / physiology*
  • Vesicular Monoamine Transport Proteins / metabolism

Substances

  • Biogenic Monoamines
  • Dopamine Plasma Membrane Transport Proteins
  • Ephrin-A5
  • Slc18a2 protein, mouse
  • Vesicular Monoamine Transport Proteins