title: Thalamic afferents influence cortical progenitors via ephrin A5-EphA4 interactions.
abstract: The phenotype of excitatory cerebral cortex neurons is specified at the progenitor level, orchestrated by various intrinsic and extrinsic factors. Here, we provide evidence for a subcortical contribution to cortical progenitor regulation by thalamic axons via ephrin A5-EphA4 interactions. Ephrin A5 is expressed by thalamic axons and represents a high-affinity ligand for EphA4 receptors detected in cortical precursors. Recombinant ephrin A5-Fc protein, as well as ephrin A ligand-expressing, thalamic axons affect the output of cortical progenitor division in vitro. Ephrin A5-deficient mice show an altered division mode of radial glial cells (RGCs) accompanied by increased numbers of intermediate progenitor cells (IPCs) and an elevated neuronal production for the deep cortical layers at E13.5. In turn, at E16.5 the pool of IPCs is diminished, accompanied by reduced rates of generated neurons destined for the upper cortical layers. This correlates with extended infragranular layers at the expense of superficial cortical layers in adult ephrin A5-deficient and EphA4-deficient mice. We suggest that ephrin A5 ligands imported by invading thalamic axons interact with EphA4-expressing RGCs, thereby contributing to the fine-tuning of IPC generation and thus the proper neuronal output for cortical layers.
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany Institute for General Zoology and Animal Physiology, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Gerstmann
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pensold
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Judit
authors.initials: J
authors.lastname: Symmank
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Mukhran
authors.initials: M
authors.lastname: Khundadze
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Hübner
authors.affiliation: Institute for General Zoology and Animal Physiology, Friedrich-Schiller-University Jena, 07743 Jena, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bolz
authors.affiliation: Institute of Human Genetics, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany Institute for General Zoology and Animal Physiology, Friedrich-Schiller-University Jena, 07743 Jena, Germany geraldine.zimmer@med.uni-jena.de.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Zimmer
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division; D002540:Cerebral Cortex / Q000166:cytology*; D004622:Embryo, Mammalian / Q000166:cytology; D063928:Ependymoglial Cells / Q000166:cytology / Q000378:metabolism; D036386:Ephrin-A5 / Q000172:deficiency / Q000378:metabolism*; D008024:Ligands; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009475:Neurons, Afferent / Q000166:cytology* / Q000378:metabolism*; D036122:Receptor, EphA4 / Q000172:deficiency / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology* / Q000196:embryology / Q000378:metabolism
chemical_list: D036386:Ephrin-A5; D008024:Ligands; D036122:Receptor, EphA4
keywords: Cortex; Ephrin A5; Neurogenesis; Thalamus