Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons.
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.
Causeret
Frédéric
F
INSERM U106, Hôpital de la Salpêtrière, 75013 Paris, France.
Danne
François
F
Ezan
Frédéric
F
Sotelo
Constantino
C
Bloch-Gallego
Evelyne
E
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
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