Robo1 and 2 repellent receptors cooperate to guide facial neuron cell migration and axon projections in the embryonic mouse hindbrain

Abstract

BackgroundThe facial nerve is necessary for our ability to eat, speak, and make facial expressions. Both the axons and cell bodies of the facial nerve undergo a complex embryonic migration pattern involving migration of the cell bodies caudally and tangentially through rhombomeres, and simultaneously the axons projecting to exit the hindbrain to form the facial nerve.\n\nResultsOur goal in this study was to test the functions of the chemorepulsive receptors Robo1 and Robo2 in facial neuron and axon migration by analyzing genetically marked motor neurons in double mutant mouse embryos through the migration time course, E10.0-E13.5. In Robo1/2 double mutants, axon and cell body migration errors were more severe than in single mutants. Most axons did not make it to their motor exit point, and instead projected into and longitudinally within the floor plate. Surprisingly, some facial neurons had bifurcated axons that either exited or projected into the floor plate. At the same time, a subset of mutant facial cell bodies failed to migrate caudally, and instead shifted into the floor plate.\n\nConclusionsRobo1 and Robo2 have redundant functions to guide multiple aspects of the complex cell migration of the facial nucleus, as well as regulating axon trajectories and suppressing formation of ectopic axons.\n\nBullet pointsO_LIRobo1 and 2 repellent receptors were tested for functions in facial neuron cell body and axon migration in the developing E10.0-E13.5 hindbrain of double mutant mouse embryos.\nC_LIO_LIIn Robo1;Robo2 double mutant embryos, facial motor neuron cell bodies and axons abnormally grew into the hindbrain floor plate, with stronger effects than in single Robo mutants.\nC_LIO_LIMany facial nerve axons abnormally bifurcated, failed to project to their proper exit point, and instead projected longitudinally within the floor plate.\nC_LIO_LIFacial neuron cell body tangential migration was disrupted.\nC_LIO_LIRobo receptor-mediated repulsion is required for proper migration of both facial axon projections and cell body migrations.\nC_LI\n\nFunding was provided to G.S.M. by NIH R01 NS054740, R21 NS077169, and R01 EY025205. Core facilities at the University of Nevada Reno campus are supported by NIH COBREs GM103650 and GM103554, and Nevada INBRE GM103440.