Multiple roles for Robo1/2 repellent receptors in guiding the facial nucleus and nerve

Abstract

The facial nerve is necessary for our ability to eat, speak, and make facialgestures. To perform these vital functions, the nerve must accurately navigate from the hindbrain to the correct muscles during embryonic development. In the development of the facial nerve, both the cell bodies and the axons undergo specific migration patterns to assemble central neuron patterns and peripheral nerve projections to target muscles. Our goal in this study was to define the molecular signals by which the facial cell bodies and their axons correctly make this long journey. By analyzing facial neuron migration patterns in mouse embryos carrying mutations in the chemorepulsive receptors Robo1 and Robo2, we found that these proteins are necessary for guiding the cell bodies and axons of the branchiomotor aspect of the facial nerve. In mutants, most axons do not make it to their motor exit point, and instead project into the floorplate. Mutant axons thatexit the hindbrain appear misguided, with some branches becoming disorganized. In addition, a subset of mutant facial cell bodies fail to undergo the correct migratory patterns and instead appear to be misguided in various locations throughout the hindbrain. Even more, a subdivision of mutant cell bodies extend multiple long neurites far away from the normal target of facial axons. Overall, we found that Robo1/2 are important for guiding multiple aspects of the complex cell migration of the facial nucleus as well as regulating the position and number of neurites that reach the periphery