The glycosyltransferase Fringe promotes Delta-Notch signaling between neurons and glia, and is required for subtype-specific glial gene expression

Thomas, Graham B.; Meyel, Donald J. van

doi:10.1242/dev.02754

Cited by 38 publications

(54 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The DNA sequences of the amplified flanking fragments were then determined, and their location in the Drosophila genome was precisely mapped using BLAST searches at the FlyBase website against Version 5.1 of the Drosophila genome annotation. For simplicity of reporting, the sequence tags provided in supplemental , Mt14-GAL4, and lz-GAL4 (Kaminker et al 2002), UAS-nGFP (Thomas and van Meyel 2007), UAS-dlA (also known as UASp-dorsal) (Matova and Anderson 2006), ro-tau-lacZ (Garrity et al 1999), Dif 1 and Dif 2 (Rutschmann et al 2000), pll 7 , pll 2 , and pll 25 (Towb et al 2001), Df(2L)J4 (Meng et al 1999).…”

Section: Methodsmentioning

confidence: 99%

A Gain-of-Function Screen for Genes That Influence Axon Guidance Identifies the NF-κB Protein Dorsal and Reveals a Requirement for the Kinase Pelle in Drosophila Photoreceptor Axon Targeting

et al. 2007

View full text Add to dashboard Cite

To identify novel regulators of nervous system development, we used the GAL4-UAS misexpression system in Drosophila to screen for genes that influence axon guidance in developing embryos. We mobilized the Gene Search (GS) P element and identified 42 lines with insertions in unique loci, including leak/roundabout2, which encodes an axon guidance receptor and confirms the utility of our screen. The genes we identified encode proteins of diverse classes, some acting near the cell surface and others in the cytoplasm or nucleus. We found that one GS line drove misexpression of the NF-kB transcription factor Dorsal, causing motor axons to bypass their correct termination sites. In the developing visual system, Dorsal misexpression also caused photoreceptor axons to reach incorrect positions within the optic lobe. This mistargeting occurred without observable changes of cell fate and correlated with localization of ectopic Dorsal in distal axons. We found that Dorsal and its inhibitor Cactus are expressed in photoreceptors, though neither was required for axon targeting. However, mutation analyses of genes known to act upstream of Dorsal revealed a requirement for the interleukin receptor-associated kinase family kinase Pelle for layerspecific targeting of photoreceptor axons, validating our screen as a means to identify new molecular determinants of nervous system development in vivo. N ERVOUS system function relies upon patterned development of neurons and controlled establishment of synaptic connections. Axons of developing neurons are guided by instructive cues to their appropriate target areas, where they then select their correct synaptic partners. Understanding how axons are guided by these cues and how they distinguish appropriate targets from inappropriate ones is a central issue in developmental neurobiology. Drosophila melanogaster has proven a successful model with which to apply genetics to this issue and study fundamental and evolutionarily conserved molecular mechanisms that underlie axon guidance. Both forward and reverse genetics approaches have been used to identify mutants with disrupted patterning of axon tracts in either the embryonic ventral nerve cord (VNC) or the developing visual system. Despite considerable successes in identifying novel genes required for axon guidance and targeting, forward genetic screening approaches can be limited by technical challenges and by genetic redundancies which obscure the detection of mutant phenotypes, undoubtedly leaving many genes and molecular pathways remaining to be described. We have exploited P-element transposition in Drosophila, combined with the GAL4-UAS gene misexpression system, to identify genes that can influence axon guidance and reveal genes that may not emerge readily from forward genetic screens. We have mobilized the Gene Search (GS) P element, which supports GAL4-directed expression of genes that flank the site of insertion (Toba et al. 1999), and screened for genes whose misexpression can influence the stereotypic patterning of emb...

show abstract

Section: Methodsmentioning

confidence: 99%

A Gain-of-Function Screen for Genes That Influence Axon Guidance Identifies the NF-κB Protein Dorsal and Reveals a Requirement for the Kinase Pelle in Drosophila Photoreceptor Axon Targeting

et al. 2007

View full text Add to dashboard Cite

show abstract

“…S3, available at www.jneurosci.org as supplemental material), indicating that a large majority of Eaat1-expressing cells are of the anterior LG subtype. This subtype also expresses Gs2 (Freeman et al, 2003;Thomas and van Meyel, 2007). Glutamine synthetases convert glutamate to glutamine, which is synaptically inert and can be safely recycled back to neurons (Hertz et al, 1999).…”

Section: Eaat1 Expression In Drosophila Cnsmentioning

confidence: 99%

“…At present, the tools available cannot distinguish the relative importance of glial cells located in the VNC versus the brain lobes. Nonetheless, Eaat1 is expressed in a limited subset of neuropil-associated glia in the VNC, including the anterior LG subtype, where it is coexpressed with the glutamate recycling enzyme Gs2 (Freeman et al, 2003;Thomas and van Meyel, 2007) and its expression is regulated by the glycosyltransferase Fng. Fng sensitizes the Notch receptor on the anterior LG to stimulation from developing axons bearing the Delta ligand and thereby promotes neuron-to-glial signaling during embryogenesis .…”

Section: Differentiation Of Functionally Distinct Glial Cell Subtypesmentioning

confidence: 99%

DrosophilaGlial Glutamate Transporter Eaat1 Is Regulated by Fringe-Mediated Notch Signaling and Is Essential for Larval Locomotion

Stacey¹,

Muraro²,

Peco³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

In the mammalian CNS, glial cells expressing excitatory amino acid transporters (EAATs) tightly regulate extracellular glutamate levels to control neurotransmission and protect neurons from excitotoxic damage. Dysregulated EAAT expression is associated with several CNS pathologies in humans, yet mechanisms of EAAT regulation and the importance of glutamate transport for CNS development and function in vivo remain incompletely understood. Drosophila is an advanced genetic model with only a single high-affinity glutamate transporter termed Eaat1. We found that Eaat1 expression in CNS glia is regulated by the glycosyltransferase Fringe, which promotes neuron-to-glia signaling through the Delta-Notch ligand-receptor pair during embryogenesis. We made Eaat1 loss-of-function mutations and found that homozygous larvae could not perform the rhythmic peristaltic contractions required for crawling. We found no evidence for excitotoxic cell death or overt defects in the development of neurons and glia, and the crawling defect could be induced by postembryonic inactivation of Eaat1. Eaat1 fully rescued locomotor activity when expressed in only a limited subpopulation of glial cells situated near potential glutamatergic synapses within the CNS neuropil. Eaat1 mutants had deficits in the frequency, amplitude, and kinetics of synaptic currents in motor neurons whose rhythmic patterns of activity may be regulated by glutamatergic neurotransmission among premotor interneurons; similar results were seen with pharmacological manipulations of glutamate transport. Our findings indicate that Eaat1 expression is promoted by Fringe-mediated neuron-glial communication during development and suggest that Eaat1 plays an essential role in regulating CNS neural circuits that control locomotion in Drosophila.

show abstract

“…Although this effect on PROS expression may be a secondary result of a cell-fate transformation, it could also be interpreted as a more direct effect of Notch signaling on pros transcription. In a different context, PROS expression has been shown to be affected by DL-activated Notch signaling in a subset of glial cells in the embryonic CNS (Thomas and van Meyel, 2007).…”

Section: A Coordinated Program For Cone-cell Inductionmentioning

confidence: 99%

Hindsight modulates Delta expression duringDrosophilacone cell induction

2009

View full text Add to dashboard Cite

The induction of cone cells in the Drosophila larval eye disc by the determined R1/R6 photoreceptor precursor cells requires integration of the Delta-Notch and EGF receptor signaling pathways with the activity of the Lozenge transcription factor. Here, we demonstrate that the zinc-finger transcription factor Hindsight (HNT) is required for normal cone-cell induction. R-cells in which hindsight levels are knocked down using RNAi show normal subtype specification, but these cells have lower levels of the Notch ligand Delta. We show that HNT functions in the determined R1/R6 precursor cells to allow Delta transcription to reach high enough levels at the right time to induce the cone-cell determinants Prospero and D-Pax2 in neighboring cells. The Delta signal emanating from the R1/R6 precursor cells is also required to specify the R7 precursor cell by repressing seven-up. As hindsight mutants have normal R7 cell-fate determination, we infer that there is a lower threshold of Delta required for R7 specification than for cone-cell induction.

show abstract

The glycosyltransferase Fringe promotes Delta-Notch signaling between neurons and glia, and is required for subtype-specific glial gene expression

Cited by 38 publications

References 92 publications

A Gain-of-Function Screen for Genes That Influence Axon Guidance Identifies the NF-κB Protein Dorsal and Reveals a Requirement for the Kinase Pelle in Drosophila Photoreceptor Axon Targeting

A Gain-of-Function Screen for Genes That Influence Axon Guidance Identifies the NF-κB Protein Dorsal and Reveals a Requirement for the Kinase Pelle in Drosophila Photoreceptor Axon Targeting

DrosophilaGlial Glutamate Transporter Eaat1 Is Regulated by Fringe-Mediated Notch Signaling and Is Essential for Larval Locomotion

Hindsight modulates Delta expression duringDrosophilacone cell induction

Contact Info

Product

Resources

About