Taniguchi H, Moore AW. Chromatin regulators in neurodevelopment and disease: Analysis of fly neural circuits provides insights: Networks of chromatin regulators and transcription factors underlie Drosophila neurogenesis and cognitive defects in intellectual disability and neuropsychiatric disorder models. Bioessays. 2014 Jul 28. PMID: 25067789.
At least the following disabilities, disorders or syndromes are mentioned in the review (Blogger does not allow tagging the entry with so many characters): Intellectual disability, Schizophrenia, Autism, CHARGE syndrome, Coffin-Siris syndrome, Kabuki syndrome, Kleefstra syndrome, Maat-Kievit-Brunner syndrome, Nicolaides-Baraitser syndrome, Rubinstein-Taybi syndrome, Say-Barber-Biesecker-Young-Simpson syndrome, Schinzel-Giedion syndrome, Sotos syndrome, Weaver syndrome, Wiedemann-Steiner syndrome
Wednesday, July 30, 2014
Wednesday, July 23, 2014
Research article and dispatch--Cancer-related study in flies
Herranz H, Weng R, Cohen SM. Crosstalk between Epithelial and Mesenchymal Tissues in Tumorigenesis and Imaginal Disc Development. Curr Biol. 2014 Jul 7;24(13):1476-84. PMID: 24980505.
From the abstract: "... Here, we report a Drosophila genetic model of EGFR-driven tumorigenesis in which the neoplastic transformation depends on interaction between epithelial and mesenchymal cells. ... Tumorigenesis in this model co-opts a regulatory mechanism that is normally involved in controlling growth of the imaginal disc during development."
See also a dispatch on the article: Milán M. Tumor Models: Tumor-Stroma Interactions Drive Neoplastic Transformation in Drosophila. Curr Biol. 2014 Jul 21;24(14):R658-R659. PMID: 25050966.
From the abstract: "... Here, we report a Drosophila genetic model of EGFR-driven tumorigenesis in which the neoplastic transformation depends on interaction between epithelial and mesenchymal cells. ... Tumorigenesis in this model co-opts a regulatory mechanism that is normally involved in controlling growth of the imaginal disc during development."
See also a dispatch on the article: Milán M. Tumor Models: Tumor-Stroma Interactions Drive Neoplastic Transformation in Drosophila. Curr Biol. 2014 Jul 21;24(14):R658-R659. PMID: 25050966.
Review--Drosophila as a model to study nanotoxicity
Ong C, Yung LY, Cai Y, Bay BH, Baeg GH. Drosophila melanogaster as a model organism to study nanotoxicity. Nanotoxicology. 2014 Jul 22:1-8. PMID: 25051331.
From the abstract: "... The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited ... Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity ...
From the abstract: "... The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited ... Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity ...
Fly study on activity and stability of Retinoblastoma protein
Zhang L, Wei Y, Pushel I, Heinze K, Elenbaas J, Henry RW, Arnosti DN. Integrated Stability and Activity Control of the Drosophila Rbf1 Retinoblastoma Protein. J Biol Chem. 2014 Jul 21. pii: jbc.M114.586818. PMID: 25049232.
Sunday, July 20, 2014
Drosophila as an in vivo system to study possible anti-cancer effects of a peptide from soy
Jones G, Srivastava A. Understanding Lunasin's biology and potential as a cancer therapeutic by utilizing Drosophila genetics. Exp Biol Med (Maywood). 2014 May;239(5):519-28. Review. PMID: 24625440.
"Soy contains many bioactive molecules known to elicit anticancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells ... Lunasin's efficacy in an in vivo system is yet to be assessed. ... we discuss the state of knowledge with respect to Lunasin and then review some of the powerful genetic tools available in Drosophila. ..."
"Soy contains many bioactive molecules known to elicit anticancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells ... Lunasin's efficacy in an in vivo system is yet to be assessed. ... we discuss the state of knowledge with respect to Lunasin and then review some of the powerful genetic tools available in Drosophila. ..."
Fly study suggests role for cation-chloride cotransporters in glia in seizure disorders
Rusan ZM, Kingsford OA, Tanouye MA. Modeling Glial Contributions to Seizures and Epileptogenesis: Cation-Chloride Cotransporters in Drosophila melanogaster. PLoS One. 2014 Jun 27;9(6):e101117. PMID: 24971529; PMCID: PMC4074161.
From the abstract: "Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. ... Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. ... The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed."
From the abstract: "Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. ... Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. ... The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed."
Study of FDA-approved drugs in flies points to possible combined therapies for cancer treatment
Markstein M, Dettorre S, Cho J, Neumüller RA, Craig-Müller S, Perrimon N. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4530-5. PMID: 24616500; PMCID: PMC3970492.
From the abstract: "Here we report the development of an in vivo system to study the interaction of stem cells with drugs using a tumor model in the adult Drosophila intestine. ... These results reveal an unanticipated side effect on stem cells that may contribute to tumor recurrence. ... An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence."
From the abstract: "Here we report the development of an in vivo system to study the interaction of stem cells with drugs using a tumor model in the adult Drosophila intestine. ... These results reveal an unanticipated side effect on stem cells that may contribute to tumor recurrence. ... An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence."
Succinate Dehydrogenase-related neurodegeneration and cancers--study in yeast, flies and mammalian cells
Van Vranken JG, Bricker DK, Dephoure N, Gygi SP, Cox JE, Thummel CS, Rutter J. SDHAF4 Promotes Mitochondrial Succinate Dehydrogenase Activity and Prevents Neurodegeneration. Cell Metab. 2014 Jun 18. pii: S1550-4131(14)00220-4. PMID: 24954416.
From the abstract: "Succinate dehydrogenase (SDH) occupies a central place in cellular energy production, linking the tricarboxylic cycle with the electron transport chain. As a result, a subset of cancers and neuromuscular disorders result from mutations affecting any of the four SDH structural subunits or either of two known SDH assembly factors. Herein we characterize an evolutionarily conserved SDH assembly factor designated Sdh8/SDHAF4, using yeast, Drosophila, and mammalian cells. ... These studies provide insights into the mechanisms by which SDH is assembled and raise the possibility that some forms of neuromuscular disease may be associated with mutations that affect this SDH assembly factor."
From the abstract: "Succinate dehydrogenase (SDH) occupies a central place in cellular energy production, linking the tricarboxylic cycle with the electron transport chain. As a result, a subset of cancers and neuromuscular disorders result from mutations affecting any of the four SDH structural subunits or either of two known SDH assembly factors. Herein we characterize an evolutionarily conserved SDH assembly factor designated Sdh8/SDHAF4, using yeast, Drosophila, and mammalian cells. ... These studies provide insights into the mechanisms by which SDH is assembled and raise the possibility that some forms of neuromuscular disease may be associated with mutations that affect this SDH assembly factor."
Catching up on neurodegenerative disease-related reports--Parkinson's disease, Fragile X syndrome, ALS
Parkinson's disease
Chuang CL, Lu YN, Wang HC, Chang HY. Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival. Hum Mol Genet. 2014 Jun 10. PMID: 24916379. [fly and rat studies]
Hwang RD, Wiemerslage L, LaBreck CJ, Khan M, Kannan K, Wang X, Zhu X, Lee D, Fridell YW. The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease. Neurobiol Dis. 2014 Sep;69:180-91. PMID: 24965893.
Ivatt RM, Whitworth AJ. SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease. Autophagy. 2014 Jun 27;10(8). Review. PMID: 24991824.
Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014 Jun 19;510(7505):370-5. PMID: 24896179.
Fragile X syndrome
He F, Krans A, Freibaum BD, Taylor JP, Todd PK. TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with HnRNP A2/B1. Hum Mol Genet. 2014 May 8. PMID: 24920338. [From the abstract: "... suggest a convergence of pathogenic cascades between repeat expansion disorders and RNA-binding proteins implicated in neurodegenerative disease."]
Friedman SH, Dani N, Rushton E, Broadie K. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila. Dis Model Mech. 2013 Nov;6(6):1400-13. PMID: 24046358; PMCID: PMC3820263.
ALS
Miskiewicz K, Jose LE, Yeshaw WM, Valadas JS, Swerts J, Munck S, Feiguin F, Dermaut B, Verstreken P. HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release. Cell Rep. 2014 Jul 10;8(1):94-102. PMID: 24981865.
Chuang CL, Lu YN, Wang HC, Chang HY. Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival. Hum Mol Genet. 2014 Jun 10. PMID: 24916379. [fly and rat studies]
Hwang RD, Wiemerslage L, LaBreck CJ, Khan M, Kannan K, Wang X, Zhu X, Lee D, Fridell YW. The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease. Neurobiol Dis. 2014 Sep;69:180-91. PMID: 24965893.
Ivatt RM, Whitworth AJ. SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease. Autophagy. 2014 Jun 27;10(8). Review. PMID: 24991824.
Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014 Jun 19;510(7505):370-5. PMID: 24896179.
Fragile X syndrome
He F, Krans A, Freibaum BD, Taylor JP, Todd PK. TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with HnRNP A2/B1. Hum Mol Genet. 2014 May 8. PMID: 24920338. [From the abstract: "... suggest a convergence of pathogenic cascades between repeat expansion disorders and RNA-binding proteins implicated in neurodegenerative disease."]
Friedman SH, Dani N, Rushton E, Broadie K. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila. Dis Model Mech. 2013 Nov;6(6):1400-13. PMID: 24046358; PMCID: PMC3820263.
ALS
Miskiewicz K, Jose LE, Yeshaw WM, Valadas JS, Swerts J, Munck S, Feiguin F, Dermaut B, Verstreken P. HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release. Cell Rep. 2014 Jul 10;8(1):94-102. PMID: 24981865.
Study explores Nedd4 role in fly and rat models of Parkinson's disease
Davies SE, Hallett PJ, Moens T, Smith G, Mangano E, Kim HT, Goldberg AL, Liu JL, Isacson O, Tofaris GK. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiol Dis. 2014 Apr;64:79-87. PMID: 24388974; PMCID: PMC3988924.
Effects of gene knockdown and polyphenol gallic acid in a fly model of Parkinson's disease
Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C. Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson's disease model. Genet Mol Biol. 2013 Dec;36(4):608-15. PMID: 24385865; PMCID: PMC3873193.
Diabetes-related fly study: from human GWAS data to fly disease model
He BZ, Ludwig MZ, Dickerson DA, Barse L, Arun B, Vilhjálmsson BJ, Jiang P, Park SY, Tamarina NA, Selleck SB, Wittkopp PJ, Bell GI, Kreitman M. Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin. Genetics. 2014 Feb;196(2):557-67. PMID: 24281155; PMCID: PMC3914626.
From the abstract: "The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. ... In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease."
From the abstract: "The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. ... In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease."
Fly study points to mechanisms for the Netrin and Deleted in Colorectal Carcinoma (DCC) proteins
Manhire-Heath R, Golenkina S, Saint R, Murray MJ. Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila. Nat Commun. 2013;4:2790. PMID: 24225841.
From the abstract: "Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC). Here we report that Netrins can also regulate epithelial dissociation during Drosophila wing eversion. ... we provide evidence that Frazzled acts through the ERM-family protein Moesin to inhibit eversion. This mechanism may also help explain the role of Netrin and DCC in cancer metastasis."
From the abstract: "Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC). Here we report that Netrins can also regulate epithelial dissociation during Drosophila wing eversion. ... we provide evidence that Frazzled acts through the ERM-family protein Moesin to inhibit eversion. This mechanism may also help explain the role of Netrin and DCC in cancer metastasis."
Fly studies help define conserved gene networks related to intellectual disability
Now free in PubMed Central:
Oortveld MA, Keerthikumar S, Oti M, Nijhof B, Fernandes AC, Kochinke K, Castells-Nobau A, van Engelen E, Ellenkamp T, Eshuis L, Galy A, van Bokhoven H, Habermann B, Brunner HG, Zweier C, Verstreken P, Huynen MA, Schenck A. Human intellectual disability genes form conserved functional modules in Drosophila. PLoS Genet. 2013 Oct;9(10):e1003911. PMID: 24204314; PMCID: PMC3814316.
From the abstract: “Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. ... Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules.”
Oortveld MA, Keerthikumar S, Oti M, Nijhof B, Fernandes AC, Kochinke K, Castells-Nobau A, van Engelen E, Ellenkamp T, Eshuis L, Galy A, van Bokhoven H, Habermann B, Brunner HG, Zweier C, Verstreken P, Huynen MA, Schenck A. Human intellectual disability genes form conserved functional modules in Drosophila. PLoS Genet. 2013 Oct;9(10):e1003911. PMID: 24204314; PMCID: PMC3814316.
From the abstract: “Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. ... Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules.”
Saturday, July 19, 2014
Fly as a model for studying wound healing--review article
Muñoz-Soriano V, López-Domenech S, Paricio N. Why mammalian wound healing researchers may wish to turn to Drosophila as a model. Exp Dermatol. 2014 Jun 18. doi: 10.1111/exd.12472. PMID: 24942366.
From the abstract: "In this paper, we discuss the benefits and limitations of using Drosophila in wound healing research, especially presenting this organism as a promising tool for the identification of new therapeutic targets and drugs in this context."
From the abstract: "In this paper, we discuss the benefits and limitations of using Drosophila in wound healing research, especially presenting this organism as a promising tool for the identification of new therapeutic targets and drugs in this context."
Tuesday, July 15, 2014
Prickle modulation of vesicle transport--relevance to seisure disorders
Big thanks to the BDSC for the heads up on this paper related to seizure disorders.
Salleh N. Ehaideb, Atulya Iyengar, Atsushi Ueda, Gary J. Iacobucci, Cathryn Cranston, Alexander G. Bassuk, David Gubb, Jeffrey D. Axelrod, Shermali Gunawardena, Chun-Fang Wua, and J. Robert Manaka (2014) prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies. PNAS.
From the abstract: "Recent analyses in flies, mice, zebrafish, and humans showed that mutations in prickle orthologs result in epileptic phenotypes, although the mechanism responsible for generating the seizures was unknown. Here, we show that Prickle organizes microtubule polarity and affects their growth dynamics in axons of Drosophila neurons, which in turn influences both anterograde and retrograde vesicle transport. ... These data reveal a previously unidentified pathway in the pathophysiology of seizure disorders and provide evidence for a more generalized cellular mechanism whereby Prickle mediates polarity by influencing microtubule-mediated transport."
Salleh N. Ehaideb, Atulya Iyengar, Atsushi Ueda, Gary J. Iacobucci, Cathryn Cranston, Alexander G. Bassuk, David Gubb, Jeffrey D. Axelrod, Shermali Gunawardena, Chun-Fang Wua, and J. Robert Manaka (2014) prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies. PNAS.
From the abstract: "Recent analyses in flies, mice, zebrafish, and humans showed that mutations in prickle orthologs result in epileptic phenotypes, although the mechanism responsible for generating the seizures was unknown. Here, we show that Prickle organizes microtubule polarity and affects their growth dynamics in axons of Drosophila neurons, which in turn influences both anterograde and retrograde vesicle transport. ... These data reveal a previously unidentified pathway in the pathophysiology of seizure disorders and provide evidence for a more generalized cellular mechanism whereby Prickle mediates polarity by influencing microtubule-mediated transport."
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