N-Cadherin Regulates Target Specificity in the Drosophila Visual System

Lee, Chi-Hon; Herman, Tory; Clandinin, Thomas R.; Lee, Roger; Zipursky, S. Lawrence

doi:10.1016/s0896-6273(01)00291-4

Cited by 249 publications

(267 citation statements)

References 47 publications

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“…R7 terminals show extensive contacts with each other before segregation into separate columns. Given the expression of a number of cell adhesion molecules such as N-Cadherin and Chaoptin on R7 terminals throughout development (Van Vactor et al, 1988;Lee et al, 2001), it seems clear that a repulsive force or an anti-adhesion mechanism is necessary to overcome the adhesion and thus facilitate the segregation of adjacent R7 terminals. Mutual repulsion has been suggested to be required for columnar restriction of L1 neurons in the Drosophila visual system, which is mediated by Dscam2 (Millard et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila

Ferguson

Hong²,

Cameron³

et al. 2009

J. Neurosci.

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Restriction of adjacent same-type axons/dendrites to separate single columns for specific neuronal connections is commonly observed in vertebrates and invertebrates, and is necessary for proper processing of sensory information. Columnar restriction is conceptually similar to tiling, a phenomenon referring to the avoidance of neurites from adjacent same-type neurons. The molecular mechanism underlying the establishment of columnar restriction or axonal/dendritic tiling remains largely undefined. Here, we identify Turtle (Tutl), a member of the conserved Tutl/Dasm1/IgSF9 subfamily of the Ig superfamily, as a key player in regulating the tiling pattern of R7 photoreceptor terminals in Drosophila. Tutl functions to prevent fusion between two adjacent R7 terminals, and acts in parallel to the Activin pathway. Tutl mediates homophilic cell-cell interactions. We propose that extrinsic terminal-terminal recognition mediated by Tutl, acts in concert with intrinsic Activin-dependent control of terminal growth, to restrict the connection made by each R7 axon to a single column.

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Section: Discussionmentioning

confidence: 99%

The Conserved Ig Superfamily Member Turtle Mediates Axonal Tiling in Drosophila

Ferguson

Hong²,

Cameron³

et al. 2009

J. Neurosci.

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“…PM181-Gal4 (ref. 8) is expressed in R7 photoreceptors, and mδ-GAL4 (generated by P. Garrity; Massachusetts Institute of Technology) is expressed in R3/R4 photoreceptors. Both lines were independently combined with the reporter line UAS-mCD8-GFP 24 and used both to examine photoreceptor neurons in the third larval stage and as a marker for cell sorting.…”

Section: Methodsmentioning

confidence: 99%

“…The mδ promoter drives expression in R3/R4 photoreceptors that project to the lamina region 7 (Fig. 2b,c), and the PM181 promoter labels R7 photoreceptors that project to the medulla 8 (Fig. 2d,e).…”

Section: Dscam Expression In Different Cell Typesmentioning

confidence: 99%

Stochastic yet biased expression of multiple Dscam splice variants by individual cells

et al. 2004

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The Drosophila melanogaster gene Dscam is essential for axon guidance and has 38,016 possible alternative splice forms. This diversity can potentially be used to distinguish cells. We analyzed the Dscam mRNA isoforms expressed by different cell types and individual cells. The choice of splice variants expressed is regulated both spatially and temporally. Different subtypes of photoreceptors express broad yet distinctive spectra of Dscam isoforms. Single-cell RT-PCR documented that individual cells express several different Dscam isoforms and allowed an estimation of the diversity that is present. For example, we estimate that each R3/R4 photoreceptor cell expresses 14-50 distinct mRNAs chosen from the spectrum of thousands of splice variants distinctive of its cell type. Thus, the Dscam repertoire of each cell is different from those of its neighbors, providing a potential mechanism for generating unique cell identity in the nervous system and elsewhere. To circumvent these technical difficulties, we used an approach that combined a customized oligonucleotide microarray, isolation of distinct populations of cells and sensitive RT-PCR that allowed examination of Dscam expression by single cells. Here we show that Dscam alternative splicing is differentially regulated both during development and in different tissues. A given cell type expresses a broad, yet distinctive, spectrum of splice variants. Individual cells express a unique repertoire of Dscam splice variants. We estimate that individual R3/R4 photoreceptors express 14-50 distinct mRNA molecules chosen from a subset of thousands of Dscam isoforms characteristic of the population. This would ensure that the Dscam repertoire of each cell is different from those of its neighbors. A R T I C L E S RESULTS A microarray for analyzing Dscam alternative splicingThe genomic structure of Dscam 1 is shown in Figure 1a. There are four alternatively spliced exons. In this study we focused on three alternatively spliced exons, which may create many possible isoforms (Fig. 1a): the cluster in exon 4 has 12 alternative exons, the cluster in exon 6 has 48 alternative exons and the cluster in exon 9 has 33 alternative exons. Each of these highly variable exons can form a portion of an immunoglobulin domain in the extracellular region of the protein. We designed a microarray containing probes for all 93 alternative exons in these three clusters. We amplified cloned DNAs (whose identities were confirmed by sequencing) by PCR to create a reference library that equally represents all the alternative exons present in the microarray. To test the specificity of the different probes in the microarray, we used combinations of RNAs in controlled amounts (Fig. 1b). RNA samples were in vitro transcribed from cloned cDNAs containing different combinations of exons 4, 6 and 9. We carried out a quantitative analysis of four independent experiments in which eight different samples were combined in different amounts spanning two orders of magnitude. Throughout this study, we expressed sample...

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“…In Drosophila N-cad is essential for target specificity of visual axons in the compound eye (Lee et al, 2001). Recently, Lele et al (2002) analyzed zebrafish parachute/n-cadherin mutants and demonstrated that N-cad is required for morphogenesis and maintained integrity of the neural tube.…”

Section: Introductionmentioning

confidence: 99%