title: Ephrin-A2 and ephrin-A5 guide contralateral targeting but not topographic mapping of ventral cochlear nucleus axons.
abstract: BACKGROUND
  In the auditory brainstem, ventral cochlear nucleus (VCN) axons project to the contralateral, but not ipsilateral, medial nucleus of trapezoid body (MNTB), terminating in the calyx of Held. Dorsal VCN neurons, representing high frequencies, synapse with medial MNTB neurons, while low frequency-coding ventral VCN neurons synapse with lateral MNTB neurons, reflecting tonotopic organization. The mechanisms that ensure strictly contralateral targeting and topographic ordering are incompletely understood. Here we examined the roles of ephrin-A signaling in both types of targeting.
  
  
  RESULTS
  Ephrin-A2 and ephrin-A5 are expressed in VCN cells during late embryonic and early postnatal development. At these ages ephrin-A2 is expressed in axons surrounding MNTB and ephrin-A5 is expressed in MNTB principal neurons. Ephrin-A2/A5 double knockout mice displayed axon targeting errors in which VCN axons project to MNTB on both sides of the brainstem, where they terminate in calyceal endings. Ephrin-A2 and ephrin-A5 single knockout mice showed a similar phenotype. In contrast to effects on contralateral targeting, ephrin-A2/A5 double knockout mice showed no defects in formation of tonotopically ordered projections from VCN to MNTB.
  
  
  CONCLUSIONS
  These findings demonstrate that distinct mechanisms regulate targeting of VCN axons to the contralateral MNTB and targeting to appropriate tonotopic locations. Ephrin-A signaling plays a similar role to ephrin-B signaling in the VCN-MNTB pathway, where both classes normally prevent formation of calyceal projections to ipsilateral MNTB. These classes may rely in part on common signaling pathways.
authors.affiliation: Division of Neonatology, Department of Pediatrics, University of California, Irvine, 101 The City Drive, Orange, CA, 92868-3298, USA. mlabdull@uci.edu.
authors.forename: Mariam L
authors.initials: ML
authors.lastname: Abdul-Latif
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 2205 McGaugh Hall, Irvine, CA, 92697-4550, USA. jaayala@uci.edu.
authors.forename: Jesus A Ayala
authors.initials: JA
authors.lastname: Salazar
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 2205 McGaugh Hall, Irvine, CA, 92697-4550, USA. forsoniam@yahoo.com.
authors.forename: Sonya
authors.initials: S
authors.lastname: Marshak
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 2205 McGaugh Hall, Irvine, CA, 92697-4550, USA. mldinh@uci.edu.
authors.forename: Minhan L
authors.initials: ML
authors.lastname: Dinh
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, 2205 McGaugh Hall, Irvine, CA, 92697-4550, USA. cramerk@uci.edu.
authors.forename: Karina S
authors.initials: KS
authors.lastname: Cramer
mesh_terms: D000818:Animals; D001306:Auditory Pathways / Q000166:cytology; D001369:Axons / Q000502:physiology*; D019521:Body Patterning / Q000502:physiology*; D017626:Cochlear Nucleus / Q000166:cytology / Q000196:embryology*; D036383:Ephrin-A2 / Q000378:metabolism*; D036386:Ephrin-A5 / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D007839:Functional Laterality; D007091:Image Processing, Computer-Assisted; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*
chemical_list: D036383:Ephrin-A2; D036386:Ephrin-A5