title: Robo2 determines subtype-specific axonal projections of trigeminal sensory neurons.
abstract: How neurons connect to form functional circuits is central to the understanding of the development and function of the nervous system. In the somatosensory system, perception of sensory stimuli to the head requires specific connections between trigeminal sensory neurons and their many target areas in the central nervous system. Different trigeminal subtypes have specialized functions and downstream circuits, but it has remained unclear how subtype-specific axonal projection patterns are formed. Using zebrafish as a model system, we followed the development of two trigeminal sensory neuron subtypes: one that expresses trpa1b, a nociceptive channel important for sensing environmental chemicals; and a distinct subtype labeled by an islet1 reporter (Isl1SS). We found that Trpa1b and Isl1SS neurons have overall similar axon trajectories but different branching morphologies and distributions of presynaptic sites. Compared with Trpa1b neurons, Isl1SS neurons display reduced branch growth and synaptogenesis at the hindbrain-spinal cord junction. The subtype-specific morphogenesis of Isl1SS neurons depends on the guidance receptor Robo2. robo2 is preferentially expressed in the Isl1SS subset and inhibits branch growth and synaptogenesis. In the absence of Robo2, Isl1SS afferents acquire many of the characteristics of Trpa1b afferents. These results reveal that subtype-specific activity of Robo2 regulates subcircuit morphogenesis in the trigeminal sensory system.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. yapan@mcb.harvard.edu
authors.forename: Y Albert
authors.initials: YA
authors.lastname: Pan
authors.forename: Margaret
authors.initials: M
authors.lastname: Choy
authors.forename: David A
authors.initials: DA
authors.lastname: Prober
authors.forename: Alexander F
authors.initials: AF
authors.lastname: Schier
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D009024:Morphogenesis; D055495:Neurogenesis; D011971:Receptors, Immunologic / Q000378:metabolism*; D012249:Rhombencephalon / Q000254:growth & development / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D015398:Signal Transduction; D013116:Spinal Cord / Q000254:growth & development / Q000378:metabolism; D000074025:TRPA1 Cation Channel; D014157:Transcription Factors / Q000378:metabolism; D050051:Transient Receptor Potential Channels; D014276:Trigeminal Nerve / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development*; D029961:Zebrafish Proteins / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D007473:Ion Channels; D060850:LIM-Homeodomain Proteins; D011971:Receptors, Immunologic; D000074025:TRPA1 Cation Channel; D014157:Transcription Factors; D050051:Transient Receptor Potential Channels; D029961:Zebrafish Proteins; C063843:insulin gene enhancer binding protein Isl-1; C498889:robo2 protein, zebrafish; D000097905:Roundabout Proteins; C494579:trpa1a protein, zebrafish