title: EphA4 has distinct functionality from EphA7 in the corticothalamic system during mouse brain development.
abstract: Deciphering the molecular basis for guiding specific aspects of neocortical development remains a challenge because of the complexity of histogenic events and the vast array of protein interactions mediating these events. The Eph family of receptor tyrosine kinases is implicated in a number of neurodevelopmental activities. Eph receptors have been known to be capable of responding to several ephrin ligands within their subgroups, often eliciting similar downstream effects. However, several recent studies have indicated specificity between receptor-ligand pairs within each subfamily, the functional relevance of which is not defined. Here we show that a receptor of the EphA subfamily, EphA4, has effects distinct from those of its close relative, EphA7, in the developing brain. Both EphA4 and EphA7 interact similarly with corresponding ligands expressed in the developing neocortex. However, only EphA7 shows strong interaction with ligands in the somatosensory thalamic nuclei; EphA4 affects only cortical neuronal migration, with no visible effects on the guidance of corticothalamic (CT) axons, whereas EphA7 affects both cortical neuronal migration and CT axon guidance. Our data provide new evidence that Eph receptors in the same subfamily are not simply interchangeable but are functionally specified through selective interactions with distinct ligands in vivo. J. Comp. Neurol. 524:2080-2092, 2016. © 2015 Wiley Periodicals, Inc.
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC, 20010.
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Son
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC, 20010.|Department of Pediatrics, Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20010.
authors.forename: Kazue
authors.initials: K
authors.lastname: Hashimoto-Torii
authors.affiliation: Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut, 06510.
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
authors.affiliation: Department of Pediatrics, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, 90027.
authors.forename: Pat
authors.initials: P
authors.lastname: Levitt
authors.affiliation: Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC, 20010.|Department of Pediatrics, Pharmacology and Physiology, The George Washington University School of Medicine and Health Sciences, Washington, DC, 20010.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Torii
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism*; D036141:Receptor, EphA7 / Q000235:genetics / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
chemical_list: D008164:Luminescent Proteins; D036122:Receptor, EphA4; D036141:Receptor, EphA7
keywords: AB_10015282; AB_221569; AB_2313608; AB_514496; AB_777699; Eph receptor; cortex; corticothalamic projections; ephrin; nif-0000-30467; rid_000042; thalamus