An axon scaffold induced by retinal axons directs glia to destinations in the<i>Drosophila</i>optic lobe

Dearborn, Richard E.; Kunes, Sam

doi:10.1242/dev.01111

Cited by 71 publications

(76 citation statements)

References 47 publications

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“…Previous studies demonstrate complex interactions between R-cell axons and laminal glial cells: R-cell axons induce the differentiation and migration of laminal glial cells (Perez and Steller 1996;Suh et al 2002;Dearborn and Kunes 2004), and conversely laminal glial cells present a stop signal for terminating R1-R6 axons within the lamina (Poeck et al 2001). To determine the potential effect of bur mutations on the development of laminal glial cells, we stained the thirdinstar optic lobe using a monoclonal antibody that recognizes the glial-specific nuclear protein Repo.…”

Section: Identification and Characterization Of The Bur Genementioning

confidence: 99%

De Novo GMP Synthesis Is Required for Axon Guidance in Drosophila

Hong

Cameron

et al. 2006

Genetics

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Guanine nucleotides are key players in mediating growth-cone signaling during neural development. The supply of cellular guanine nucleotides in animals can be achieved via the de novo synthesis and salvage pathways. The de novo synthesis of guanine nucleotides is required for lymphocyte proliferation in animals. Whether the de novo synthesis pathway is essential for any other cellular processes, however, remains unknown. In a search for genes required for the establishment of neuronal connectivity in the fly visual system, we identify the burgundy (bur) gene as an essential player in photoreceptor axon guidance. The bur gene encodes the only GMP synthetase in Drosophila that catalyzes the final reaction of de novo GMP synthesis. Loss of bur causes severe defects in axonal fasciculation, retinotopy, and growth-cone morphology, but does not affect photoreceptor differentiation or retinal patterning. Similar defects were observed when the raspberry (ras) gene, encoding for inosine monophosphate dehydrogenase catalyzing the IMP-to-XMP conversion in GMP de novo synthesis, was mutated. Our study thus provides the first in vivo evidence to support an essential and specific role for de novo synthesis of guanine nucleotides in axon guidance.

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Section: Identification and Characterization Of The Bur Genementioning

confidence: 99%

De Novo GMP Synthesis Is Required for Axon Guidance in Drosophila

Hong

Cameron

et al. 2006

Genetics

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“…It is also during this stage that 90% of neurons in the adult CNS of Drosophila are generated (Arama et al 2000;Bello et al 2006Bello et al , 2007. Glial differentiation during the third instar larval stage occurs in the optic stalk and glia precursor cell areas (GPC), which are located in the dorsal and ventral margins of the optic ganglion (Poeck et al 2001;Dearborn and Kunes 2004). On the basis of position, morphology, and function, third instar larval brain glia are classified into three subtypes: (1) surface glia, (2) cortex glia, and (3) neuropile glia.…”

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confidence: 99%

Regulation of Glia Number in Drosophila by Rap/Fzr, an Activator of the Anaphase-Promoting Complex, and Loco, an RGS Protein

2008

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Glia mediate a vast array of cellular processes and are critical for nervous system development and function. Despite their immense importance in neurobiology, glia remain understudied and the molecular mechanisms that direct their differentiation are poorly understood. Rap/Fzr is the Drosophila homolog of the mammalian Cdh1, a regulatory subunit of the anaphase-promoting complex/cyclosome (APC/C). APC/C is an E3 ubiquitin ligase complex well characterized for its role in cell cycle progression. In this study, we have uncovered a novel cellular role for Rap/Fzr. Loss of rap/fzr function leads to a marked increase in the number of glia in the nervous system of third instar larvae. Conversely, ectopic expression of UAS-rap/fzr, driven by repo-GAL4, results in the drastic reduction of glia. Data from clonal analyses using the MARCM technique show that Rap/Fzr regulates the differentiation of surface glia in the developing larval nervous system. Our genetic and biochemical data further indicate that Rap/Fzr regulates glial differentiation through its interaction with Loco, a regulator of G-protein signaling (RGS) protein and a known effector of glia specification. We propose that Rap/Fzr targets Loco for ubiquitination, thereby regulating glial differentiation in the developing nervous system.

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“…Lack of connectivity at the optic lobe also results in massive optic lobe neuronal death [16,17] due to abnormal function originating from the retina rather than the brain [16,17]. A trophic factor for retinal neurons is predicted to emanate from the brain optic lobe glia [16,17]. In the embryonic CNS, upon glial ablation or mutations in glial cells missing, there is excess neuronal apoptosis [18].…”

Section: Introductionmentioning

confidence: 99%

Drosophila neurotrophins reveal a common mechanism for nervous system formation

Zhu¹,

Pennack²,

McQuilton³

et al. 2008

SciVee

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Neurotrophic interactions occur in Drosophila, but to date, no neurotrophic factor had been found. Neurotrophins are the main vertebrate secreted signalling molecules that link nervous system structure and function: they regulate neuronal survival, targeting, synaptic plasticity, memory and cognition. We have identified a neurotrophic factor in flies, Drosophila Neurotrophin (DNT1), structurally related to all known neurotrophins and highly conserved in insects. By investigating with genetics the consequences of removing DNT1 or adding it in excess, we show that DNT1 maintains neuronal survival, as more neurons die in DNT1 mutants and expression of DNT1 rescues naturally occurring cell death, and it enables targeting by motor neurons. We show that Spä tzle and a further fly neurotrophin superfamily member, DNT2, also have neurotrophic functions in flies. Our findings imply that most likely a neurotrophin was present in the common ancestor of all bilateral organisms, giving rise to invertebrate and vertebrate neurotrophins through gene or whole-genome duplications. This work provides a missing link between aspects of neuronal function in flies and vertebrates, and it opens the opportunity to use Drosophila to investigate further aspects of neurotrophin function and to model related diseases.Citation: Zhu B, Pennack JA, McQuilton P, Forero MG, Mizuguchi K, et al. (2008) Drosophila neurotrophins reveal a common mechanism for nervous system formation. PLoS Biol 6(11): e284.

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An axon scaffold induced by retinal axons directs glia to destinations in theDrosophilaoptic lobe

Cited by 71 publications

References 47 publications

De Novo GMP Synthesis Is Required for Axon Guidance in Drosophila

De Novo GMP Synthesis Is Required for Axon Guidance in Drosophila

Regulation of Glia Number in Drosophila by Rap/Fzr, an Activator of the Anaphase-Promoting Complex, and Loco, an RGS Protein

Drosophila neurotrophins reveal a common mechanism for nervous system formation

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