Wrapper, a Novel Member of the Ig Superfamily, Is Expressed by Midline Glia and Is Required for Them to Ensheath Commissural Axons in Drosophila

Noordermeer, Jasprina N.; Kopczynski, Casey; Fetter, Richard D.; Bland, Kimberly S.; Chen, Wei-Yu; Goodman, Corey S.

doi:10.1016/s0896-6273(00)80618-2

Cited by 113 publications

(138 citation statements)

References 44 publications

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“…Midline glia include three pairs of cells, the anterior (MGA), medial (MGM), and posterior (MGP) midline glia. Wrapper is a marker for midline glia that is predominantly expressed at the surface of MGA and MGM (Noordermeer et al, 1998). By using combined in situ and antibody staining, we could detect vav transcripts in all Wrapper-expressing cells.…”

Section: Resultsmentioning

confidence: 93%

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

Malartre

Ayaz²,

Amador³

et al. 2010

J. Neurosci.

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The Vav proteins are guanine exchange factors (GEFs) that trigger the activation of the Rho GTPases in general and the Rac family in particular. While the role of the mammalian vav genes has been extensively studied in the hematopoietic system and the immune response, there is little information regarding the role of vav outside of these systems. Here, we report that the single Drosophila vav homolog is ubiquitously expressed during development, although it is enriched along the embryonic ventral midline and in the larval eye discs and brain. We have analyzed the role that vav plays during development by generating Drosophila null mutant alleles. Our results indicate that vav is required during embryogenesis to prevent longitudinal axons from crossing the midline. Later on, during larval development, vav is required within the axons to regulate photoreceptor axon targeting to the optic lobe. Finally, we demonstrate that adult vav mutant escapers, which exhibit coordination problems, display axon growth defects in the ellipsoid body, a brain area associated with locomotion control. In addition, we show that vav interacts with other GEFs known to act downstream of guidance receptors. Thus, we propose that vav acts in coordination with other GEFs to regulate axon growth and guidance during development by linking guidance signals to the cytoskeleton via the modulation of Rac activity.

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Section: Resultsmentioning

confidence: 93%

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

Malartre

Ayaz²,

Amador³

et al. 2010

J. Neurosci.

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“…The following antibodies were used on formaldehyde-fixed embryos: mouse monoclonal antibody (mAb) BP102 (gift of C. Goodman, University of California, Berkeley, CA), rabbit anti-MYC (Upstate), rabbit anti-GFP (Invitrogen), mouse mAb anti-Wrapper (Noordermeer et al, 1998), mouse mAb anti-REPO (Alfonso and Jones, 2002) and rabbit anti-SRC64B (gift of T. Xu, Yale University, New Haven, CT). Rabbit anti-SRC64B peptide antibody (Muda et al, 2002) was used to stain the larval neuropiles expressing SRC64B in motoneurons.…”

Section: Immunohistochemistry and Rna In Situ Hybridizationmentioning

confidence: 99%

Src family kinases are required for WNT5 signaling through the Derailed/RYK receptor in theDrosophilaembryonic central nervous system

et al. 2008

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Members of the RYK/Derailed family have recently been shown to regulate axon guidance in both Drosophila and mammals by acting as Wnt receptors. Little is known about how the kinase activity-deficient RYKs transduce Wnt signals. Here, we show that the non-receptor Src family tyrosine kinases, SRC64B and SRC42A, are involved in WNT5-mediated signaling through Derailed in the Drosophila embryonic central nervous system. Analysis of animals lacking SRC64B and SRC42A reveals defects in commissure formation similar to those observed in Wnt5 and derailed mutants. Reductions in SRC64B expression levels suppress a Wnt5/derailed-dependent dominant gain-of-function phenotype, and increased levels of either SRC64B or SRC42A enhance Wnt5/derailed-mediated axon commissure switching. Derailed and SRC64B form a complex, which contains catalytically active SRC64B, the formation or stability of which requires SRC64B kinase activity. Furthermore, Derailed is phosphorylated in a SRC64B-dependent manner and coexpression of Derailed and SRC64B results in the activation of SRC64B. The mammalian orthologs of Derailed and SRC64B also form complexes, suggesting that Src roles in RYK signaling are conserved. Finally, we show that coexpression of WNT5 and Derailed has no apparent effect upon TCF/LEF-dependent transcription, suggesting that the WNT5/Derailed signaling pathway is unlikely to directly regulate canonical Wnt pathway targets. Together, these findings indicate that the Src family kinases play novel roles in WNT5/Derailed-mediated signaling.

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“…Spi is a signaling molecule that plays multiple roles during Drosophila development (for a review, see Shilo 2005). Wrapper protein is normally found on the surface of midline glia where it mediates direct contact with the lateral CNS axons that cross the midline and promotes survival of midline glia (Noordermeer et al 1998). In wrapper mutant embryos, this intimate interaction cannot occur and additional midline glia die.…”

Section: Tablementioning

confidence: 99%

“…In contrast, wrapper is restricted largely to midline glia, with a relatively low level of expression in some chordotonal cells of the embryo (Noordermeer et al 1998). To understand how wrapper is restricted to midline glia during Drosophila embryogenesis, we are studying its regulation, both the transcription factors that activate it and the regulatory sequences controlling its expression.…”

mentioning

confidence: 99%

Identification of Motifs That Are Conserved in 12 Drosophila Species and Regulate Midline Glia vs. Neuron Expression

2008

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Functional complexity of the central nervous system (CNS) is reflected by the large number and diversity of genes expressed in its many different cell types. Understanding the control of gene expression within cells of the CNS will help reveal how various neurons and glia develop and function. Midline cells of Drosophila differentiate into glial cells and several types of neurons and also serve as a signaling center for surrounding tissues. Here, we examine regulation of the midline gene, wrapper, required for both neuron-glia interactions and viability of midline glia. We identify a region upstream of wrapper required for midline expression that is highly conserved (87%) between 12 Drosophila species. Site-directed mutagenesis identifies four motifs necessary for midline glial expression: (1) a Single-minded/Tango binding site, (2) a motif resembling a pointed binding site, (3) a motif resembling a Sox binding site, and (4) a novel motif. An additional highly conserved 27 bp are required to restrict expression to midline glia and exclude it from midline neurons. These results suggest short, highly conserved genomic sequences flanking Drosophila midline genes are indicative of functional regulatory regions and that small changes within these sequences can alter the expression pattern of a gene.

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Wrapper, a Novel Member of the Ig Superfamily, Is Expressed by Midline Glia and Is Required for Them to Ensheath Commissural Axons in Drosophila

Cited by 113 publications

References 44 publications

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

The Guanine Exchange FactorvavControls Axon Growth and Guidance duringDrosophilaDevelopment

Src family kinases are required for WNT5 signaling through the Derailed/RYK receptor in theDrosophilaembryonic central nervous system

Identification of Motifs That Are Conserved in 12 Drosophila Species and Regulate Midline Glia vs. Neuron Expression

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