Genetic Analysis of TOR Signaling in Drosophila

Neufeld, Thomas

doi:10.1007/978-3-642-18930-2_9

Cited by 22 publications

(20 citation statements)

References 48 publications

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“…Target of rapamycin (Tor) and insulin receptor (InR) signaling pathways monitor nutrient status and mediate cell growth in animals ( Fig. 4A) (for reviews, see Long et al, 2004;Neufeld, 2004). An intriguing new study reveals that increased signaling through the Tor/InR pathways causes precocious neuronal differentiation, whereas reduced activity delays differentiation (Bateman and McNeill, 2004).…”

Section: Nutritional Inputs Into Developmental Timingmentioning

confidence: 99%

Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues

Rougvie

2005

Development

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A fundamental challenge in biology is to understand the reproducibility of developmental programs between individuals of the same metazoan species. This developmental precision reflects the meticulous integration of temporal control mechanisms with those that specify other aspects of pattern formation, such as spatial and sexual information. The cues that guide these developmental events are largely intrinsic to the organism but can also include extrinsic inputs, such as nutrition or temperature. This review discusses the well-characterized developmental timing mechanism that patterns the C. elegans epidermis. Components of this pathway are conserved, and their links to developmental time control in other species are considered, including the temporal patterning of the fly nervous system. Particular attention is given to the roles of miRNAs in developmental timing and to the emerging mechanisms that link developmental programs to nutritional cues. Summary

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Section: Nutritional Inputs Into Developmental Timingmentioning

confidence: 99%

Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues

Rougvie

2005

Development

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“…The fact that the majority of InR/ PI3K and Tor pathway mutants fail to dominantly modify the small-wing phenotype may be simply because these gene products are not limiting for wing growth, at least under conditions in which InR/PI3K signaling is already impaired. Tor itself may be an exception to this general observation because it promotes growth in response to multiple inputs and has several growthregulatory targets (Neufeld 2004; see discussion).…”

Section: Characterization Of the Ms1096dp110mentioning

confidence: 99%

“…In response to high levels of nutrients and/or growth factors, Tor stimulates S6 kinase and the translation initiation factor eIF-4E and is thought to promote growth, at least in part, through upregulation of protein synthesis (reviewed in Neufeld 2004). CycD-Cdk4 is remarkable in that it promotes cellular growth and cell cycle progression in a coordinated manner and can therefore increase overall organ size Meyer et al 2000).…”

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confidence: 99%

A Genetic Screen for Dominant Modifiers of a Small-Wing Phenotype in Drosophila melanogaster Identifies Proteins Involved in Splicing and Translation

et al. 2005

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Studies in the fly, Drosophila melanogaster, have revealed that several signaling pathways are important for the regulation of growth. Among these, the insulin receptor/phosphoinositide 3-kinase (PI3K) pathway is remarkable in that it affects growth and final size without disturbing pattern formation. We have used a small-wing phenotype, generated by misexpression of kinase-dead PI3K, to screen for novel mutations that specifically disrupt organ growth in vivo. We identified several complementation groups that dominantly enhance this small-wing phenotype. Meiotic recombination in conjunction with visible markers and single-nucleotide polymorphisms (SNPs) was used to map five enhancers to single genes. Two of these, nucampholin and prp8, encode pre-mRNA splicing factors. The three other enhancers encode factors required for mRNA translation: pixie encodes the Drosophila ortholog of yeast RLI1, and RpL5 and RpL38 encode proteins of the large ribosomal subunit. Interestingly, mutations in several other ribosomal protein-encoding genes also enhance the small-wing phenotype used in the original screen. Our work has therefore identified mutations in five previously uncharacterized Drosophila genes and provides in vivo evidence that normal organ growth requires optimal regulation of both pre-mRNA splicing and mRNA translation.

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“…The fruit fly Drosophila has proven to be an important system for understanding the molecular mechanisms of Tsc-Rheb-Tor signaling during development [7]. As in vertebrates, this signaling cascade is a critical regulator of growth.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance

Knox

Dimitroff

et al. 2007

PLoS ONE

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Tuberous sclerosis complex is a dominant genetic disorder produced by mutations in either of two tumor suppressor genes, TSC1 and TSC2; it is characterized by hamartomatous tumors, and is associated with severe neurological and behavioral disturbances. Mutations in TSC1 or TSC2 deregulate a conserved growth control pathway that includes Ras homolog enriched in brain (Rheb) and Target of Rapamycin (TOR). To understand the function of this pathway in neural development, we have examined the contributions of multiple components of this pathway in both neuromuscular junction assembly and photoreceptor axon guidance in Drosophila. Expression of Rheb in the motoneuron, but not the muscle of the larval neuromuscular junction produced synaptic overgrowth and enhanced synaptic function, while reductions in Rheb function compromised synapse development. Synapse growth produced by Rheb is insensitive to rapamycin, an inhibitor of Tor complex 1, and requires wishful thinking, a bone morphogenetic protein receptor critical for functional synapse expansion. In the visual system, loss of Tsc1 in the developing retina disrupted axon guidance independently of cellular growth. Inhibiting Tor complex 1 with rapamycin or eliminating the Tor complex 1 effector, S6 kinase (S6k), did not rescue axon guidance abnormalities of Tsc1 mosaics, while reductions in Tor function suppressed those phenotypes. These findings show that Tsc-mediated control of axon guidance and synapse assembly occurs via growth-independent signaling mechanisms, and suggest that Tor complex 2, a regulator of actin organization, is critical in these aspects of neuronal development.

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Genetic Analysis of TOR Signaling in Drosophila

Cited by 22 publications

References 48 publications

Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues

Intrinsic and extrinsic regulators of developmental timing: from miRNAs to nutritional cues

A Genetic Screen for Dominant Modifiers of a Small-Wing Phenotype in Drosophila melanogaster Identifies Proteins Involved in Splicing and Translation

Mechanisms of TSC-mediated Control of Synapse Assembly and Axon Guidance

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