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|Title:||CONTROL OF SPINAL MOTOR NEURON MYOTOPIC ORGANIZATION BY REELIN SIGNALING |
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|Authors/Affiliations:||2 Elena Palmesino*; 2 Tzu-Jen Kao; 1 Avihu Klar ; 3 Artur Kania; |
1 Department of Anatomy and Cell Biology, Hebrew University Medical School; 2 Institut de recherches cliniques de Montréal (IRCM) ; 3 Institut de recherches cliniques de Montréal (IRCM), Departement of Anatomy and Cell Biology, Division of Experimental Medicine, McGill University and Faculty of Medicine, Université de Montréal, QC, Canada
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|Content:||Objectives: The development of topographic neuronal maps involves the coordinated control of soma localization and axon pathfinding. To understand this process, we study the development of the binary topography of the lateral motor column (LMC) located in the ventral spinal cord: lateral LMC neurons innervate dorsal limb muscles, whereas medial LMC neurons innervate ventral limb muscles. These subpopulations are distinguished by their respective expression of the LIM homeodomain proteins LIM1 and ISL1. In addition to controlling LMC axon projections, these transcription factors are sufficient to specify the medio-lateral localisation of LMC somata, suggesting that they may also regulate the expression of effectors mediating LMC cell body positioning. The Reelin pathway is a critical effector of neuronal migration; we thus hypothesize that in LMC neurons, LIM homeodomain proteins coordinate soma localisation with axonal trajectory selection by regulating the expression of members of the Reelin signaling pathway.|
Material and Methods: To establish whether LMC cell body position is controlled by Reelin signaling, we determined the expression profile of its signaling components by in situ mRNA hybridization and immunohistochemistry and analyzed the effect of their loss of function in chick and mouse embryonic spinal cords.
Results and conclusions: Reelin expression is adjacent to LMC neurons that express the Reelin receptor VLDLR. Interestingly, the gene encoding the intracellular adaptor protein DAB1, relaying Reelin signaling, is expressed at higher level in lateral LMC neurons than in medial LMC neurons. Reeler and Dab1 mutant mice and chick embryos overexpressing a mutated form of DAB1 show abnormal localisation of lateral LMC motor neurons providing evidence that Reelin signaling functions to establish the myotopic organization of LMC neurons. We are currently testing the hypothesis that the LIM homeodomain proteins ISL1 and LIM1 coordinate lateral and medial LMC motor neuron position by their modulation of the Reelin signaling pathway.
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