Slit antagonizes netrin-1 attractive effects during the migration of inferior olivary neurons |
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Authors: | Causeret Frédéric Danne François Ezan Frédéric Sotelo Constantino Bloch-Gallego Evelyne |
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Institution: | INSERM U106, H?pital de la Salpêtrière, 75013 Paris, France. |
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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. |
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Keywords: | nuclear translocation axon outgrowth brainstem floor-plate precerebellar nuclei chemotropic molecules robo receptors collagen assays in situ hybridization mice |
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