title: Contralateral migration of oculomotor neurons is regulated by Slit/Robo signaling.
abstract: Oculomotor neurons develop initially like typical motor neurons, projecting axons out of the ventral midbrain to their ipsilateral targets, the extraocular muscles. However, in all vertebrates, after the oculomotor nerve (nIII) has reached the extraocular muscle primordia, the cell bodies that innervate the superior rectus migrate to join the contralateral nucleus. This motor neuron migration represents a unique strategy to form a contralateral motor projection. Whether migration is guided by diffusible cues remains unknown.
  
  
  
  We examined the role of Slit chemorepellent signals in contralateral oculomotor migration by analyzing mutant mouse embryos.
  
  
  
  We found that the ventral midbrain expresses high levels of both Slit1 and 2, and that oculomotor neurons express the repellent Slit receptors Robo1 and Robo2. Therefore, Slit signals are in a position to influence the migration of oculomotor neurons. In Slit 1/2 or Robo1/2 double mutant embryos, motor neuron cell bodies migrated into the ventral midbrain on E10.5, three days prior to normal migration. These early migrating neurons had leading projections into and across the floor plate. In contrast to the double mutants, embryos which were mutant for single Slit or Robo genes did not have premature migration or outgrowth on E10.5, demonstrating a cooperative requirement of Slit1 and 2, as well as Robo1 and 2. To test how Slit/Robo midline repulsion is modulated, we found that the normal migration did not require the receptors Robo3 and CXCR4, or the chemoattractant, Netrin 1. The signal to initiate contralateral migration is likely autonomous to the midbrain because oculomotor neurons migrate in embryos that lack either nerve outgrowth or extraocular muscles, or in cultured midbrains that lacked peripheral tissue.
  
  
  
  Overall, our results demonstrate that a migratory subset of motor neurons respond to floor plate-derived Slit repulsion to properly control the timing of contralateral migration.
authors: Department of Biology, University of Nevada, Reno, NV, 89557, USA.
authors: Brielle
authors: B
authors: Bjorke
authors: Department of Biology, University of Nevada, Reno, NV, 89557, USA.
authors: Farnaz
authors: F
authors: Shoja-Taheri
authors: Department of Biology, University of Nevada, Reno, NV, 89557, USA.
authors: Minkyung
authors: M
authors: Kim
authors: Department of Biology, University of Nevada, Reno, NV, 89557, USA.
authors: G Eric
authors: GE
authors: Robinson
authors: Department of Biology, University of Nevada, Reno, NV, 89557, USA.
authors: Tatiana
authors: T
authors: Fontelonga
authors: School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju, 500-712, Republic of Korea.
authors: Kyung-Tai
authors: KT
authors: Kim
authors: School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju, 500-712, Republic of Korea.
authors: Mi-Ryoung
authors: MR
authors: Song
authors: Department of Biology, University of Nevada, Reno, NV, 89557, USA. gmastick@unr.edu.
authors: Grant S
authors: 0000-0002-9148-6194
authors: GS
authors: Mastick
mesh_terms: D000818:Animals; D000071437:Axon Guidance; D002465:Cell Movement; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D008636:Mesencephalon / Q000502:physiology; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*; D009414:Nerve Growth Factors / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology*; D000075388:Netrin-1; D009802:Oculomotor Nerve / Q000254:growth & development*; D019718:Receptors, CXCR4 / Q000502:physiology; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D000075388:Netrin-1; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D025521:Tumor Suppressor Proteins; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C514936:CXCR4 protein, mouse; C000617353:Ntn1 protein, mouse; C498888:Robo2 protein, mouse; C118348:Robo3 protein, mouse; C120010:Slit1 protein, mouse
keywords: Floor plate; Migration; Motor neuron; Oculomotor; Slit/Robo