title: The Formin DAAM Functions as Molecular Effector of the Planar Cell Polarity Pathway during Axonal Development in Drosophila.
abstract: Recent studies established that the planar cell polarity (PCP) pathway is critical for various aspects of nervous system development and function, including axonal guidance. Although it seems clear that PCP signaling regulates actin dynamics, the mechanisms through which this occurs remain elusive. Here, we establish a functional link between the PCP system and one specific actin regulator, the formin DAAM, which has previously been shown to be required for embryonic axonal morphogenesis and filopodia formation in the growth cone. We show that dDAAM also plays a pivotal role during axonal growth and guidance in the adult Drosophila mushroom body, a brain center for learning and memory. By using a combination of genetic and biochemical assays, we demonstrate that Wnt5 and the PCP signaling proteins Frizzled, Strabismus, and Dishevelled act in concert with the small GTPase Rac1 to activate the actin assembly functions of dDAAM essential for correct targeting of mushroom body axons. Collectively, these data suggest that dDAAM is used as a major molecular effector of the PCP guidance pathway. By uncovering a signaling system from the Wnt5 guidance cue to an actin assembly factor, we propose that the Wnt5/PCP navigation system is linked by dDAAM to the regulation of the growth cone actin cytoskeleton, and thereby growth cone behavior, in a direct way.
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, H-6726, Szeged, Hungary, Hungarian Academy of Sciences, Office for Subsidized Research Units, Budapest, H-1051, Hungary, and.
authors.forename: Rita
authors.initials: R
authors.lastname: Gombos
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, H-6726, Szeged, Hungary.
authors.forename: Ede
authors.identifier: http://orcid.org/0000-0002-8312-6463
authors.initials: E
authors.lastname: Migh
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, H-6726, Szeged, Hungary.
authors.forename: Otilia
authors.identifier: http://orcid.org/0000-0001-8321-5039
authors.initials: O
authors.lastname: Antal
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Anindita
authors.initials: A
authors.lastname: Mukherjee
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jenny
authors.affiliation: Institute of Genetics, Biological Research Centre HAS, H-6726, Szeged, Hungary, Hungarian Academy of Sciences, Office for Subsidized Research Units, Budapest, H-1051, Hungary, and mihaly.jozsef@brc.mta.hu.
authors.forename: József
authors.initials: J
authors.lastname: Mihály
mesh_terms: D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D016764:Cell Polarity / Q000235:genetics*; D000072261:Dishevelled Proteins; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D020439:Growth Cones / Q000502:physiology; D047468:Immunoprecipitation; D024521:Mushroom Bodies / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D051153:Wnt Proteins / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C509803:DAAM protein, Drosophila; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C090146:Rac1 protein, Drosophila; D014157:Transcription Factors; D051153:Wnt Proteins; C491438:Wnt5 protein, Drosophila; C000606588:dsh protein, Drosophila; D020744:rac GTP-Binding Proteins
keywords: Drosophila; PCP; axon growth; dDAAM; formin; mushroom body