title: Detection of ligands in regions anatomically connected to neurons expressing the Eph receptor Bsk: potential roles in neuron-target interaction.
abstract: Neuron-target interaction is a key feature in the establishment of neuronal networks. However, the underlying mechanism remains unclear. We have shown that at the time of target innervation, Bsk, an eph family receptor, is expressed at high levels in several brain regions including the hippocampus, olfactory bulb, and retina. To study whether the ligands are expressed in the target tissues, we investigated the expression of Bsk ligands using a ligand-affinity probe, Bsk-AP, which consisted of the extracellular domain of Bsk fused in frame with a human placental alkaline phosphatase. These analyses showed that the ligands were expressed at high levels in the developing septum, hypothalamus, olfactory neural epithelium, and tectum. In situ hybridization studies revealed that at least three different factors were responsible for the Bsk-AP binding. In the septum, Elf-1, Lerk3 (Eff-2), and AL-1/Lerk7 were transcribed. In the hypothalamus, AL-1/Lerk7 was the ligand detected by Bsk-AP. In the olfactory system, high levels of Lerk3 were detected in the sensory neurons. Both Elf-1 and AL-1/Lerk7 were present in the tectum. These ligand-positive areas are known to be anatomically connected to Bsk-expressing regions. These observations strongly suggest that Bsk and the ligands participate in neuron-target interactions in multiple systems and provide support for their involvement in topographic projection.
authors.affiliation: Department of Chemical Biology, College of Pharmacy, Rutgers University, Piscataway, New Jersey 08855, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Zhang
authors.forename: D P
authors.initials: DP
authors.lastname: Cerretti
authors.forename: T
authors.initials: T
authors.lastname: Yu
authors.forename: J G
authors.initials: JG
authors.lastname: Flanagan
authors.forename: R
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000469:Alkaline Phosphatase; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology*; D001923:Brain Chemistry / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics; D036383:Ephrin-A2; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000201:enzymology; D006801:Humans; D017403:In Situ Hybridization; D008024:Ligands; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000737:chemistry* / Q000201:enzymology*; D009687:Nuclear Proteins; D009830:Olfactory Bulb / Q000166:cytology / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D036123:Receptor, EphA5; D017978:Receptors, Growth Factor / Q000502:physiology*; D012686:Septal Nuclei / Q000166:cytology / Q000201:enzymology; D013477:Superior Colliculi / Q000166:cytology / Q000201:enzymology; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C512897:ELF1 protein, human; C512896:Elf1 protein, mouse; D036383:Ephrin-A2; D008024:Ligands; D008565:Membrane Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D014157:Transcription Factors; D020794:Receptor Protein-Tyrosine Kinases; D036123:Receptor, EphA5; D000469:Alkaline Phosphatase