title: Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons.
abstract: Inferior olivary neurons (ION) migrate circumferentially around the caudal rhombencephalon starting from the alar plate to locate ventrally close to the floor-plate, ipsilaterally to their site of proliferation. The floor-plate constitutes a source of diffusible factors. Among them, netrin-1 is implied in the survival and attraction of migrating ION in vivo and in vitro. We have looked for a possible involvement of slit-1/2 during ION migration. We report that: (1) slit-1 and slit-2 are coexpressed in the floor-plate of the rhombencephalon throughout ION development; (2) robo-2, a slit receptor, is expressed in migrating ION, in particular when they reach the vicinity of the floor-plate; (3) using in vitro assays in collagen matrix, netrin-1 exerts an attractive effect on ION leading processes and nuclei; (4) slit has a weak repulsive effect on ION axon outgrowth and no effect on migration by itself, but (5) when combined with netrin-1, it antagonizes part of or all of the effects of netrin-1 in a dose-dependent manner, inhibiting the attraction of axons and the migration of cell nuclei. Our results indicate that slit silences the attractive effects of netrin-1 and could participate in the correct ventral positioning of ION, stopping the migration when cell bodies reach the floor-plate.
authors.affiliation: INSERM U106, Hôpital de la Salpêtrière, 75013 Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Causeret
authors.forename: François
authors.initials: F
authors.lastname: Danne
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ezan
authors.forename: Constantino
authors.initials: C
authors.lastname: Sotelo
authors.forename: Evelyne
authors.initials: E
authors.lastname: Bloch-Gallego
mesh_terms: D000818:Animals; D001369:Axons; D002465:Cell Movement; D018920:Coculture Techniques; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D009414:Nerve Growth Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D000075388:Netrin-1; D009474:Neurons / Q000378:metabolism*; D009847:Olivary Nucleus / Q000166:cytology* / Q000196:embryology; D025521:Tumor Suppressor Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617353:Ntn1 protein, mouse; C120010:Slit1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D000098552:Slit Homolog 2 Protein