title: Robo1 and robo2 control the development of the lateral olfactory tract.
abstract: The development of olfactory bulb projections that form the lateral olfactory tract (LOT) is still poorly understood. It is known that the septum secretes Slit1 and Slit2 which repel olfactory axons in vitro and that in Slit1-/-;Slit2-/- mutant mice, the LOT is profoundly disrupted. However, the involvement of Slit receptors, the roundabout (Robo) proteins, in guiding LOT axons has not been demonstrated. We show here that both Robo1 and Robo2 receptors are expressed on early developing LOT axons, but that only Robo2 is present at later developmental stages. Olfactory bulb axons from Robo1-/-;Robo2-/- double-mutant mice are not repelled by Slit in vitro. The LOT develops normally in Robo1-/- mice, but is completely disorganized in Robo2-/- and Robo1-/-;Robo2-/- double-mutant embryos, with many LOT axons spreading along the ventral surface of the telencephalon. Finally, the position of lot1-expressing cells, which have been proposed to be the LOT guidepost cells, appears unaffected in Slit1-/-;Slit2-/- mice and in Robo1-/-;Robo2-/- mice. Together, our results indicate that Robo1 and Robo2 directly mediate the repulsive activity of Slit receptors on LOT axons, and are required for normal guidance of these axons in vivo.
authors.affiliation: Centre National de la Recherche Scientifique and Université Pierre et Marie Curie-Paris 6, Unité Mixte de Recherche 7102, Paris, 75005 France.
authors.forename: Coralie
authors.initials: C
authors.lastname: Fouquet
authors.forename: Thomas
authors.initials: T
authors.lastname: Di Meglio
authors.forename: Le
authors.initials: L
authors.lastname: Ma
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Hua
authors.initials: H
authors.lastname: Long
authors.forename: Tatsumi
authors.initials: T
authors.lastname: Hirata
authors.forename: Marc
authors.initials: M
authors.lastname: Tessier-Lavigne
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
authors.forename: Kim T
authors.initials: KT
authors.lastname: Nguyen-Ba-Charvet
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009830:Olfactory Bulb / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D009833:Olfactory Pathways / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D000097905:Roundabout Proteins
chemical_list: D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C498888:Robo2 protein, mouse