title: The seven-pass transmembrane cadherin Flamingo controls dendritic self-avoidance via its binding to a LIM domain protein, Espinas, in Drosophila sensory neurons.
abstract: Members of the Flamingo cadherin family are required in a number of different in vivo contexts of neural development. Even so, molecular identities downstream from the family have been poorly understood. Here we show that a LIM domain protein, Espinas (Esn), binds to an intracellular juxtamembrane domain of Flamingo (Fmi), and that this Fmi-Esn interplay elicits repulsion between dendritic branches of Drosophila sensory neurons. In wild-type larvae, branches of the same class IV dendritic arborization neuron achieve efficient coverage of its two-dimensional receptive field with minimum overlap with each other. However, this self-avoidance was disrupted in a fmi hypomorphic mutant, in an esn knockout homozygote, and in the fmi/esn trans-heterozygote. A functional fusion protein, Fmi:3eGFP, was localized at most of the branch tips, and in a heterologous system, assembly of Esn at cell contact sites required its LIM domain and Fmi. We further show that genes controlling epithelial planar cell polarity (PCP), such as Van Gogh (Vang) and RhoA, are also necessary for the self-avoidance, and that fmi genetically interacts with these loci. On the basis of these and other results, we propose that the Fmi-Esn complex, together with the PCP regulators and the Tricornered (Trc) signaling pathway, executes the repulsive interaction between isoneuronal dendritic branches.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsubara
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Horiuchi
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimono
authors.forename: Tadao
authors.initials: T
authors.lastname: Usui
authors.forename: Tadashi
authors.initials: T
authors.lastname: Uemura
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D055786:Gene Knockout Techniques; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011984:Sensory Receptor Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; C562135:Esn protein, Drosophila; D009419:Nerve Tissue Proteins; C121420:stan protein, Drosophila