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Hox Paralog Group 2 Genes Control the Migration of Mouse Pontine Neurons through Slit-Robo Signaling

PLoS Biology
Public Library of Science
Publication Date
DOI: 10.1371/journal.pbio.0060142
  • Research Article
  • Developmental Biology
  • Neuroscience
  • Ecology
  • Geography


Author Summary In the developing central nervous system, neurons migrate sometimes over long distances from their birthplace to their final location, where they condense in specific nuclei. The precise positioning of migrating neurons is critical to the building of ordered connectivity with their target partners. Little is known about how exposure of migrating neurons to simultaneous attractive and repulsive guidance cues may be integrated at the transcriptional level and in turn translated into directional migratory responses specific for each neuronal population. Here, we focus on the molecular mechanisms regulating the directionality of long-distance migration of pontine neurons in the mouse brainstem. Such neurons belong to the so-called precerebellar system, which is essential for coordinated motor activity, and provide the principal input to the cerebellum. We provide evidence for the implication of homeodomain transcription factors of the Hox gene family in the control of pontine neuron migration along the brain rostrocaudal axis. We identify the guidance receptor Robo2 as a direct target gene of the Hoxa2 gene. We further show that repulsive signaling mediated through the Robo2 receptor expressed in migrating neurons and its ligand Slit2 secreted from the facial motor nucleus are key components of the molecular guidance system that maintains caudorostral migration and prevents premature attraction towards the brainstem ventral midline. Our data provide a conceptual framework to understand how transcriptional regulation of the response to environmental guidance cues controls stereotyped neuronal migratory behavior in the developing mammalian brain.

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