title: Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain.
abstract: The floor plate is known to be a source of repellent signals for cranial motor axons, preventing them from crossing the midline of the hindbrain. However, it is unknown which molecules mediate this effect in vivo. We show that Slit and Robo proteins are candidate motor axon guidance molecules, as Robo proteins are expressed by cranial motoneurons, and Slit proteins are expressed by the tissues that delimit motor axon trajectories, i.e. the floor plate and the rhombic lip. We present in vitro evidence showing that Slit1 and Slit2 proteins are selective inhibitors and repellents for dorsally projecting, but not for ventrally projecting, cranial motor axons. Analysis of mice deficient in Slit and Robo function shows that cranial motor axons aberrantly enter the midline, while ectopic expression of Slit1 in chick embryos leads to specific motor axon projection errors. Expression of dominant-negative Robo receptors within cranial motoneurons in chick embryos strikingly perturbs their projections, causing some motor axons to enter the midline, and preventing dorsally projecting motor axons from exiting the hindbrain. These data suggest that Slit proteins play a key role in guiding dorsally projecting cranial motoneurons and in facilitating their neural tube exit.
authors.affiliation: MRC Centre for Developmental Neurobiology, 4th Floor New Hunt's House, King's College, Guy's Campus, London SE1 1UL, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Hammond
authors.forename: Valerie
authors.initials: V
authors.lastname: Vivancos
authors.forename: Arifa
authors.initials: A
authors.lastname: Naeem
authors.forename: John
authors.initials: J
authors.lastname: Chilton
authors.forename: Elvira
authors.initials: E
authors.lastname: Mambetisaeva
authors.forename: Elvira
authors.initials: E
authors.lastname: Mambitisaeva
authors.forename: William
authors.initials: W
authors.lastname: Andrews
authors.forename: Vasi
authors.initials: V
authors.lastname: Sundaresan
authors.forename: Sarah
authors.initials: S
authors.lastname: Guthrie
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D012249:Rhombencephalon / Q000196:embryology* / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C120566:slit protein, vertebrate