title: Sema-1a Reverse Signaling Promotes Midline Crossing in Response to Secreted Semaphorins.
abstract: Commissural axons must cross the midline to form functional midline circuits. In the invertebrate nerve cord and vertebrate spinal cord, midline crossing is mediated in part by Netrin-dependent chemoattraction. Loss of crossing, however, is incomplete in mutants for Netrin or its receptor Frazzled/DCC, suggesting the existence of additional pathways. We identified the transmembrane Semaphorin, Sema-1a, as an important regulator of midline crossing in the Drosophila CNS. We show that in response to the secreted Semaphorins Sema-2a and Sema-2b, Sema-1a functions as a receptor to promote crossing independently of Netrin. In contrast to other examples of reverse signaling where Sema1a triggers repulsion through activation of Rho in response to Plexin binding, in commissural neurons Sema-1a acts independently of Plexins to inhibit Rho to promote attraction to the midline. These findings suggest that Sema-1a reverse signaling can elicit distinct axonal responses depending on differential engagement of distinct ligands and signaling effectors.
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hernandez-Fleming
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA.
authors.forename: Ethan W
authors.initials: EW
authors.lastname: Rohrbach
authors.affiliation: Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA. Electronic address: gbashaw@mail.med.upenn.edu.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Bashaw
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D019521:Body Patterning / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002630:Chemotactic Factors / Q000494:pharmacology; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D005820:Genetic Testing; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000072417:Protein Domains; D039961:Semaphorins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015815:Cell Adhesion Molecules; D002630:Chemotactic Factors; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D039961:Semaphorins; C091529:plexin; C477531:semaphorin 1a, Drosophila
keywords: Drosophila; axon guidance; chemoattraction; dcc; frazzled; growth cone; midline; netrin; reverse signaling; semaphorin