title: A transcription factor network coordinates attraction, repulsion, and adhesion combinatorially to control motor axon pathway selection.
abstract: Combinations of transcription factors (TFs) instruct precise wiring patterns in the developing nervous system; however, how these factors impinge on surface molecules that control guidance decisions is poorly understood. Using mRNA profiling, we identified the complement of membrane molecules regulated by the homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron (dMN) identity in Drosophila. Combinatorial loss- and gain-of-function genetic analyses of Eve target genes indicate that the integrated actions of attractive, repulsive, and adhesive molecules direct eve-dependent dMN axon guidance. Furthermore, combined misexpression of Eve target genes is sufficient to partially restore CNS exit and can convert the guidance behavior of interneurons to that of dMNs. Finally, we show that a network of TFs, comprised of eve, zfh1, and grain, induces the expression of the Unc5 and Beaten-path guidance receptors and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN axons.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Aref Arzan
authors.initials: AA
authors.lastname: Zarin
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Asadzadeh
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Karsten
authors.initials: K
authors.lastname: Hokamp
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Daniel
authors.initials: D
authors.lastname: McCartney
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Greg J
authors.initials: GJ
authors.lastname: Bashaw
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin 2, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. Electronic address: labradoj@tcd.ie.
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Labrador
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007395:Interneurons / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism*; D009415:Nerve Net / Q000254:growth & development / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D014157:Transcription Factors