title: Ephrin-A5 exerts positive or inhibitory effects on distinct subsets of EphA4-positive motor neurons.
abstract: Eph receptor tyrosine kinases and ephrins are required for axon patterning and plasticity in the developing nervous system. Typically, Eph-ephrin interactions promote inhibitory events; for example, prohibiting the entry of neural cells into certain embryonic territories. Here, we show that distinct subsets of motor neurons that express EphA4 respond differently to ephrin-A5. EphA4-positive LMC(l) axons avoid entering ephrin-A5-positive hindlimb mesoderm. In contrast, EphA4-positive MMC(m) axons extend through ephrin-A5-positive rostral half-sclerotome. Blocking EphA4 activation in MMC(m) neurons or expanding the domain of ephrin-A5 expression in the somite results in the aberrant growth of MMC(m) axons into the caudal half-sclerotome. Moreover, premature expression of EphA4 in MMC(m) neurons leads to a portion of their axons growing into novel ephrin-A5-positive territories. Together, these results indicate that EphA4-ephrin-A5 signaling acts in a positive manner to constrain MMC(m) axons to the rostral half-sclerotome. Furthermore, we show that Eph activation localizes to distinct subcellular compartments of LMC(l) and MMC(m) neurons, consistent with distinct EphA4 signaling cascades in these neuronal subpopulations.
authors.affiliation: Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
authors.forename: Johann
authors.initials: J
authors.lastname: Eberhart
authors.forename: Jason
authors.initials: J
authors.lastname: Barr
authors.forename: Sinead
authors.initials: S
authors.lastname: O'Connell
authors.forename: Alleda
authors.initials: A
authors.lastname: Flagg
authors.forename: Mary E
authors.initials: ME
authors.lastname: Swartz
authors.forename: Karina S
authors.initials: KS
authors.lastname: Cramer
authors.forename: Kathryn W
authors.initials: KW
authors.lastname: Tosney
authors.forename: Elena B
authors.initials: EB
authors.lastname: Pasquale
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Krull
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D018274:Electroporation; D036385:Ephrin-A4 / Q000096:biosynthesis* / Q000235:genetics; D036386:Ephrin-A5 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D006614:Hindlimb / Q000196:embryology / Q000294:innervation; D008024:Ligands; D008648:Mesoderm / Q000378:metabolism; D009046:Motor Neurons / Q000187:drug effects / Q000378:metabolism*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D036385:Ephrin-A4; D036386:Ephrin-A5; D008024:Ligands