title: The homeodomain transcription factor Hb9 controls axon guidance in Drosophila through the regulation of Robo receptors.
abstract: Transcription factors establish neural diversity and wiring specificity; however, how they orchestrate changes in cell morphology remains poorly understood. The Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how their precise expression domains are established is unknown. Here, we show that the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon guidance in the Drosophila embryo. In ventrally projecting motor neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can regulate the medio-lateral position of axons through robo2 and robo3, and restoring robo3 expression in hb9 mutants rescues the lateral position defects of a subset of neurons. Altogether, these data identify Robo2 and Robo3 as key effectors of Hb9 in regulating nervous system development.
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Santiago
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Labrador
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, 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 / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000097905:Roundabout Proteins
chemical_list: D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D011971:Receptors, Immunologic; D014157:Transcription Factors; C421243:Robo2 protein, Drosophila; D000097905:Roundabout Proteins; C490005:exex protein, Drosophila; C421244:robo3 protein, Drosophila