title: Motor neuron cell bodies are actively positioned by Slit/Robo repulsion and Netrin/DCC attraction.
abstract: Motor neurons differentiate from a ventral column of progenitors and settle in static clusters, the motor nuclei, next to the floor plate. Within these cell clusters, motor neurons receive afferent input and project their axons out to muscle targets. The molecular mechanisms that position motor neurons in the neural tube remain poorly understood. The floor plate produces several types of guidance cues with well-known roles in attracting and repelling axons, including the Slit family of chemorepellents via their Robo receptors, and Netrin1 via its DCC attractive receptor. In the present study we found that Islet1(+) motor neuron cell bodies invaded the floor plate of Robo1/2 double mutant mouse embryos or Slit1/2/3 triple mutants. Misplaced neurons were born in their normal progenitor column, but then migrated tangentially into the ventral midline. Robo1 and 2 receptor expression in motor neurons was confirmed by reporter gene staining and anti-Robo antibody labeling. Mis-positioned motor neurons projected their axons longitudinally within the floor plate, and failed to reach their normal exit points. To test for potential counteracting ventral attractive signals, we examined Netrin-1 and DCC mutants, and found that motor neurons shifted dorsally in the hindbrain and spinal cord, suggesting that Netrin-1/DCC signaling normally attracts motor neurons closer to the floor plate. Our results show that motor neurons are actively migrating cells, and are normally trapped in a static position by Slit/Robo repulsion and Netrin-1/DCC attraction.
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA.
authors.forename: Minkyung
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Fontelonga
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Roesener
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA.
authors.forename: Haeram
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Gurung
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA.
authors.forename: Philipe R F
authors.initials: PRF
authors.lastname: Mendonca
authors.affiliation: Department of Biology, University of Nevada, Reno, NV, USA. Electronic address: gmastick@unr.edu.
authors.forename: Grant S
authors.initials: GS
authors.lastname: Mastick
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D066146:Cell Body / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D000075389:DCC Receptor; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000378:metabolism*; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000075388:Netrin-1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D000075389:DCC Receptor; D049452:Green Fluorescent Proteins; D060850:LIM-Homeodomain Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075388:Netrin-1; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000097905:Roundabout Proteins; C501910:Dcc protein, mouse; C000617353:Ntn1 protein, mouse; C120010:Slit1 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1
keywords: Floor plate; Migration; Motor neuron; Netrin/DCC; Slit/Robo