title: Ephrin-B/EphB Signaling Is Required for Normal Innervation of Lingual Gustatory Papillae.
abstract: The innervation of taste buds is an excellent model system for studying the guidance of axons during targeting because of their discrete nature and the high fidelity of innervation. The pregustatory epithelium of fungiform papillae is known to secrete diffusible axon guidance cues such as BDNF and Sema3A that attract and repel, respectively, geniculate ganglion axons during targeting, but diffusible factors alone are unlikely to explain how taste axon terminals are restricted to their territories within the taste bud. Nondiffusible cell surface proteins such as Ephs and ephrins can act as receptors and/or ligands for one another and are known to control axon terminal positioning in several parts of the nervous system, but they have not been studied in the gustatory system. We report that ephrin-B2 linked β-galactosidase staining and immunostaining was present along the dorsal epithelium of the mouse tongue as early as embryonic day 15.5 (E15.5), but was not detected at E14.5, when axons first enter the epithelium. Ephrin-B1 immunolabeling was barely detected in the epithelium and found at a somewhat higher concentration in the mesenchyme subjacent to the epithelium. EphB1 and EphB2 were detected in lingual sensory afferents in vivo and geniculate neurites in vitro. Ephrin-B1 and ephrin-B2 were similarly effective in repelling or suppressing outgrowth by geniculate neurites in vitro. These in vitro effects were independent of the neurotrophin used to promote outgrowth, but were reduced by elevated levels of laminin. In vivo, mice null for EphB1 and EphB2 exhibited decreased gustatory innervation of fungiform papillae. These data provide evidence that ephrin-B forward signaling is necessary for normal gustatory innervation of the mammalian tongue.
authors.affiliation: Department of Biology, Loyola University Chicago, Chicago, Ill., USA.
authors.forename: Randall William
authors.initials: RW
authors.lastname: Treffy
authors.forename: David
authors.initials: D
authors.lastname: Collins
authors.forename: Natalia
authors.initials: N
authors.lastname: Hoshino
authors.forename: Son
authors.initials: S
authors.lastname: Ton
authors.forename: Gennadiy Aleksandrovich
authors.initials: GA
authors.lastname: Katsevman
authors.forename: Michael
authors.initials: M
authors.lastname: Oleksiak
authors.forename: Elizabeth Marie
authors.initials: EM
authors.lastname: Runge
authors.forename: David
authors.initials: D
authors.lastname: Cho
authors.forename: Matthew
authors.initials: M
authors.lastname: Russo
authors.forename: Andrej
authors.initials: A
authors.lastname: Spec
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gomulka
authors.forename: Mark
authors.initials: M
authors.lastname: Henkemeyer
authors.forename: Michael William
authors.initials: MW
authors.lastname: Rochlin
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D036342:Ephrins / Q000378:metabolism*; D004848:Epithelium / Q000294:innervation / Q000378:metabolism; D005830:Geniculate Ganglion / Q000378:metabolism*; D051379:Mice; D016501:Neurites / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013650:Taste Buds / Q000378:metabolism*; D014059:Tongue / Q000294:innervation* / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D036342:Ephrins