Pioneer longitudinal axons navigate using floor plate and Slit/Robo signals.
Longitudinal axons transmit all signals between the brain and spinal cord. Their axon tracts through the brain stem are established by a simple set of pioneer axons with precise trajectories parallel to the floor plate. To identify longitudinal guidance mechanisms in vivo, the overall role of floor plate tissue and the specific roles of Slit/Robo signals were tested. Ectopic induction or genetic deletion of the floor plate diverted longitudinal axons into abnormal trajectories. The expression patterns of the diffusible cues of the Slit family were altered in the floor plate experiments, suggesting their involvement in longitudinal guidance. Genetic tests of Slit1 and Slit2, and the Slit receptors Robo1 and Robo2 were carried out in mutant mice. Slit1;Slit2 double mutants had severe longitudinal errors, particularly for ventral axons, including midline crossing and wandering longitudinal trajectories. Robo1 and Robo2 were largely genetically redundant, and neither appeared to specify specific tract positions. However, combined Robo1 and Robo2 mutations strongly disrupted each pioneer tract. Thus, pioneer axons depend on long-range floor plate cues, with Slit/Robo signaling required for precise longitudinal trajectories.
Department of Biology, University of Nevada, Reno, NV 89557, USA.
W Todd
WT
Farmer
Amy L
AL
Altick
Hikmet Feyza
HF
Nural
James P
JP
Dugan
Thomas
T
Kidd
Frédéric
F
Charron
Grant S
GS
Mastick
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000075746:Zinc Finger Protein Gli2; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D053823:Hedgehog Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000075746:Zinc Finger Protein Gli2; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C000618551:Gli2 protein, mouse; C498888:Robo2 protein, mouse; C120010:Slit1 protein, mouse