title: Drosophila N-cadherin functions in the first stage of the two-stage layer-selection process of R7 photoreceptor afferents.
abstract: Visual information received from the three types of photoreceptor neurons (R1-R6, R7 and R8) in the fly compound eyes converges to the external part of the medulla neuropil (M1-M6 layers) in a layer-specific fashion: R7 and R8 axons terminate at the M6 and M3 layers, respectively, whereas lamina neurons (L1-L5) relay R1-R6 to multiple medulla layers (M1-M5). Here, we show that during development, R7 and R8 neurons establish layer-specific projections in two separate stages: during the first stage, R7 and R8 axons sequentially target to the R7- and R8-temporary layers, respectively; and at the second stage, R7 and R8 growth cones progress synchronously to their destined layers. Using a set of mutations that delete different afferent subsets or alter R7 connectivity, we defined the mechanism of layer selection. We observed that R8, R7 and L1-L5 afferents target to their temporary layers independently, suggesting that afferent-target, but not afferent-afferent, interactions dictate the targeting specificity. N-cadherin is required in the first stage for R7 growth cones to reach and remain in the R7-temporary layer. The Ncad gene contains three pairs of alternatively spliced exons and encodes 12 isoforms. However, expressing a single Ncad isoform in Ncad mutant R7s is sufficient to rescue mistargeting phenotypes. Furthermore, Ncad isoforms mediate promiscuous heterophilic interactions in an in vitro cell-aggregation assay. We propose that Ncad isoforms do not form an adhesion code; rather, they provide permissive adhesion between R7 growth cones and their temporary targets.
authors.affiliation: Laboratory of Gene Regulation and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Ting
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yonekura
authors.forename: Phoung
authors.initials: P
authors.lastname: Chung
authors.forename: Shu-Ning
authors.initials: SN
authors.lastname: Hsu
authors.forename: Hugh M
authors.initials: HM
authors.lastname: Robertson
authors.forename: Akira
authors.initials: A
authors.lastname: Chiba
authors.forename: Chi-Hon
authors.initials: CH
authors.lastname: Lee
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001369:Axons / Q000378:metabolism; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation; D018076:DNA, Complementary / Q000378:metabolism; D004331:Drosophila melanogaster; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008954:Models, Biological; D008957:Models, Genetic; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D017956:Photoreceptor Cells, Invertebrate / Q000196:embryology*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D015820:Cadherins; D018076:DNA, Complementary; D020033:Protein Isoforms; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins