title: Flamingo, a seven-pass transmembrane cadherin, cooperates with Netrin/Frazzled in Drosophila midline guidance.
abstract: During central nervous system development, several guidance cues and receptors, as well as cell adhesion molecules, are required for guiding axons across the midline and along the anterior-posterior axis. In Drosophila, commissural axons sense the midline attractants Netrin A and B (Net) through Frazzled (Fra) receptors. Despite their importance, lack of Net or fra affects only some commissures, suggesting that additional molecules can fulfill this function. Recently, planar cell polarity (PCP) proteins have been implicated in midline axon guidance in both vertebrate and invertebrate systems. Here, we report that the atypical cadherin and PCP molecule Flamingo/Starry night (Fmi/Stan) acts jointly with Net/Fra signaling during midline development. Additional removal of fmi strongly increases the guidance defects in Net/fra mutants. Rescue and domain deletion experiments suggest that Fmi signaling facilitates commissural pathfinding potentially by mediating axonal fasciculation in a partly homophilic manner. Altogether, our results indicate that contact-mediated cell adhesion via Fmi acts in addition to the Net/Fra guidance system during axon pathfinding across the midline, underlining the importance of PCP molecules during vertebrates and invertebrates midline development.
authors.affiliation: Max Planck Institute of Neurobiology, Sensory Neurogenetics Research Group, Am Klopferspitz 18, Martinsried, 82152, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Organisti
authors.forename: Irina
authors.initials: I
authors.lastname: Hein
authors.forename: Ilona C
authors.initials: IC
authors.lastname: Grunwald Kadow
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000075386:Netrin Receptors; D000075388:Netrin-1; D000075385:Netrins; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; C562135:Esn protein, Drosophila; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C000617352:NetA protein, Drosophila; C583437:NetB protein, Drosophila; D000075386:Netrin Receptors; D000075385:Netrins; C090146:Rac1 protein, Drosophila; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C000617310:fra protein, Drosophila; C121420:stan protein, Drosophila; D000075388:Netrin-1; D011505:Protein-Tyrosine Kinases; C506548:Abl protein, Drosophila; D020744:rac GTP-Binding Proteins