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PMID:16162649

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Citation

Hammond, R, Vivancos, V, Naeem, A, Chilton, J, Mambetisaeva, E, Mambitisaeva, E, Andrews, W, Sundaresan, V and Guthrie, S (2005) Slit-mediated repulsion is a key regulator of motor axon pathfinding in the hindbrain. Development 132:4483-95

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.

Links

PubMed Online version:10.1242/dev.02038

Keywords

Animals; Axons/metabolism; Cell Line; Cells, Cultured; Chick Embryo; Electroporation; Gene Expression Regulation, Developmental; Genotype; Glycoproteins/genetics; Glycoproteins/metabolism; Humans; Mice; Motor Neurons/metabolism; Mutation/genetics; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Rats; Receptors, Immunologic/genetics; Receptors, Immunologic/metabolism; Rhombencephalon/embryology; Rhombencephalon/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:SLIT1

involved_in

GO:0008045: motor neuron axon guidance

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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