The slit receptor Rig-1/Robo3 controls midline crossing by hindbrain precerebellar neurons and axons

Neuron. 2004 Jul 8;43(1):69-79. doi: 10.1016/j.neuron.2004.06.018.

Abstract

During development, precerebellar neurons migrate dorsoventrally from the rhombic lip to the floor plate. Some of these neurons cross the midline while others stop. We have identified a role for the slit receptor Rig-1/Robo3 in directing this process. During their tangential migration, neurons of all major hindbrain precerebellar nuclei express high levels of Rig-1 mRNA. Rig-1 expression is rapidly downregulated as their leading process crosses the floor plate. Interestingly, most precerebellar nuclei do not develop normally in Rig-1-deficient mice, as they fail to cross the midline. In addition, inferior olivary neurons, which normally send axons into the contralateral cerebellum, project ipsilaterally in Rig-1 mutant mice. Similarly, neurons of the lateral reticular nucleus and basilar pons are unable to migrate across the floor plate and instead remain ipsilateral. These results demonstrate that Rig-1 controls the ability of both precerebellar neuron cell bodies and their axons to cross the midline.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cerebellum / cytology
  • Cerebellum / embryology*
  • Cerebellum / metabolism
  • Fetus
  • Functional Laterality / genetics
  • Gene Expression Regulation, Developmental / genetics
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology*
  • Neural Pathways / cytology
  • Neural Pathways / embryology*
  • Neural Pathways / metabolism
  • Olivary Nucleus / cytology
  • Olivary Nucleus / embryology
  • Olivary Nucleus / metabolism
  • Pons / cytology
  • Pons / embryology
  • Pons / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Cell Surface
  • Rhombencephalon / cytology
  • Rhombencephalon / embryology*
  • Rhombencephalon / metabolism

Substances

  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Robo3 protein, mouse
  • Slit1 protein, mouse