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Publication

Opposing Action of Hedgehog and Insulin Signaling Balances Proliferation and Autophagy to Determine Follicle Stem Cell Lifespan.

Developmental cell | 2018

Egg production declines with age in many species, a process linked with stem cell loss. Diet-dependent signaling has emerged as critical for stem cell maintenance during aging. Follicle stem cells (FSCs) in the Drosophila ovary are exquisitely responsive to diet-induced signals including Hedgehog (Hh) and insulin-IGF signaling (IIS), entering quiescence in the absence of nutrients and initiating proliferation rapidly upon feeding. Although highly proliferative FSCs generally exhibit an extended lifespan, we find that constitutive Hh signaling drives FSC loss and premature sterility despite high proliferative rates. This occurs due to Hh-mediated induction of autophagy in FSCs via a Ptc-dependent, Smo-independent mechanism. Hh-dependent autophagy increases during aging, triggering FSC loss and consequent reproductive arrest. IIS is necessary and sufficient to suppress Hh-induced autophagy, promoting a stable proliferative state. These results suggest that opposing action of diet-responsive IIS and Hh signals determine reproductive lifespan by modulating the proliferation-autophagy balance in FSCs during aging.

Pubmed ID: 30197240 RIS Download

Research resources used in this publication

Additional research tools detected in this publication

None found

Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: P30 CA006927
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM084947
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD065800

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This is a list of tools and resources that we have found mentioned in this publication.

Rabbit Anti-phospho Histone H3 (Ser28) Monoclonal Antibody, Unconjugated, Clone E191l (antibody)

RRID:AB_10807285

This monoclonal targets Rabbit phospho Histone H3 (Ser28) Clone E191l

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Vasa (d-260) (antibody)

RRID:AB_793874

This polyclonal targets Vasa (d-260)

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Cy3-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (antibody)

RRID:AB_2307443

This polyclonal targets IgG (H+L)

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Fasciclin III (Drosophila) antibody - Goodman, C.; University of California, Berkeley (antibody)

RRID:AB_528238

This monoclonal targets Fasciclin III (Drosophila)

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Cy5-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (antibody)

RRID:AB_2340607

This unknown targets Rabbit IgG (H+L)

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VECTASHIELD Mounting Medium (antibody)

RRID:AB_2336789

This unknown targets

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Alexa Fluor 647 goat anti-rat IgM (micro chain) *2 mg mL* (antibody)

RRID:AB_11180200

This unknown targets Alexa Fluor 647 goat anti-rat IgM (micro chain) *2 mg mL*

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Fluorescein (FITC)-AffiniPure Goat Anti-Chicken IgY (IgG) (H+L) (min X Bov,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rb,Rat,Shp Sr Prot) (antibody)

RRID:AB_2337384

This unknown targets Chicken IgY(IgG) (H+L)

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Fluorescein (FITC)-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Rat,Shp Sr Prot) (antibody)

RRID:AB_2335588

This polyclonal targets IgG (H+L)

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Cy3-AffiniPure Donkey Anti-Mouse IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Rb,Rat,Shp Sr Prot) (antibody)

RRID:AB_2315777

This polyclonal targets Mouse IgG (H+L)

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Rat Anti-Drosophila vasa Antibody, Unconjugated (antibody)

RRID:AB_760351

This unknown targets Rat Drosophila vasa

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beta Actin antibody - Loading Control (antibody)

RRID:AB_2305186

This polyclonal targets RCJMB04_4h19

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GFP Polyclonal Antibody (antibody)

RRID:AB_2534023

This unknown targets GFP

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P{ry[+t7.2]=hsFLP}1, y[1] w[1118]; P{w[+mC]=UAS-Atg8a.GFP}3 (organism)

RRID:BDSC_51656

Drosophila melanogaster with name P{ry[+t7.2]=hsFLP}1, y[1] w[1118]; P{w[+mC]=UAS-Atg8a.GFP}3 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00252}attP2 (organism)

RRID:BDSC_35341

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00252}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01351}attP2 (organism)

RRID:BDSC_34362

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01351}attP2 from BDSC.

View all literature mentions

ptc[tuf-1] Rab32[ltd-1] (organism)

RRID:DGGR_105908

Drosophila melanogaster with name ptc[tuf-1] Rab32[ltd-1] from DGGR.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01804}attP2 (organism)

RRID:BDSC_25794

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01804}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02786}attP2 (organism)

RRID:BDSC_27706

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02786}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02028}attP40 (organism)

RRID:BDSC_40861

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02028}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01244}attP2 (organism)

RRID:BDSC_34899

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01244}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03872}attP40 (organism)

RRID:BDSC_55686

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03872}attP40 from BDSC.

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w[*]; P{w[+mC]=UAS-ptc.J}B1 (organism)

RRID:BDSC_5817

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-ptc.J}B1 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00923}attP2 (organism)

RRID:BDSC_33966

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00923}attP2 from BDSC.

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y[1] w[1118]; P{w[+mC]=UAS-InR.A1325D}2 (organism)

RRID:BDSC_8263

Drosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-InR.A1325D}2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02897}attP2 (organism)

RRID:BDSC_28060

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02897}attP2 from BDSC.

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w[*]; P{w[+mC]=UAS-myr-Akt1.V}3/TM3, Sb[1] (organism)

RRID:BDSC_50758

Discontinued

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w[1118]; P{w[+mC]=UAS-stg.N}16 (organism)

RRID:DGGR_107872

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-stg.N}16 from DGGR.

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w[*]; P{w[+mC]=UAS-ptc.1130X}C (organism)

RRID:BDSC_44612

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-ptc.1130X}C from BDSC.

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y[1] w[*] P{ry[+t7.2]=hsFLP}12; P{w[+mC]=UAS-Tor.WT}III (organism)

RRID:BDSC_7012

Drosophila melanogaster with name y[1] w[*] P{ry[+t7.2]=hsFLP}12; P{w[+mC]=UAS-Tor.WT}III from BDSC.

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w[*]; P{w[+mC]=hs-Ilp2.R}2/CyO, amos[Roi-1] (organism)

RRID:BDSC_37472

Drosophila melanogaster with name w[*]; P{w[+mC]=hs-Ilp2.R}2/CyO, amos[Roi-1] from BDSC.

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w[*]; P{w[+mC]=UAS-Rheb.Pa}3 (organism)

RRID:BDSC_9689

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-Rheb.Pa}3 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02891}attP2 (organism)

RRID:BDSC_28055

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02891}attP2 from BDSC.

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Pka-C1[B10] (organism)

RRID:BDSC_32018

Drosophila melanogaster with name Pka-C1[B10] from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01358}attP2/TM3, Sb[1] (organism)

RRID:BDSC_34369

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01358}attP2/TM3, Sb[1] from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02706}attP2 (organism)

RRID:BDSC_27554

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02706}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01715}attP2 (organism)

RRID:BDSC_28984

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01715}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01482}attP2 (organism)

RRID:BDSC_31037

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01482}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00735}attP2 (organism)

RRID:BDSC_32941

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00735}attP2 from BDSC.

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w[1118]; P{w[+mC]=UAS-AMPKalpha.T184D}2/CyO (organism)

RRID:BDSC_32110

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-AMPKalpha.T184D}2/CyO from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02273}attP2 (organism)

RRID:BDSC_26731

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02273}attP2 from BDSC.

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w[*]; P{w[+mC]=UAS-unc-51.WT}3 (organism)

RRID:BDSC_60734

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-unc-51.WT}3 from BDSC.

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y[1]; P{ry[+t7.2]=neoFRT}42D ptc[S2]/CyO (organism)

RRID:BDSC_6332

Drosophila melanogaster with name y[1]; P{ry[+t7.2]=neoFRT}42D ptc[S2]/CyO from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HM04007}attP2 (organism)

RRID:BDSC_31701

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HM04007}attP2 from BDSC.

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Fiji (software resource)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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GraphPad Prism (software resource)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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Adobe Photoshop (software resource)

RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

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y[1] w[*]; P{w[+mC]=UAS-smo.RNAi}2 P{UAS-smo.RNAi}8/CyO, P{Wee-P.ph0}2 (organism)

RRID:BDSC_24472

Drosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-smo.RNAi}2 P{UAS-smo.RNAi}8/CyO, P{Wee-P.ph0}2 from BDSC.

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y[1] w[*]; P{w[+mW.hs]=GawB}109-30/CyO (organism)

RRID:BDSC_7023

Drosophila melanogaster with name y[1] w[*]; P{w[+mW.hs]=GawB}109-30/CyO from BDSC.

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w[*]; Pka-C1[DN]/CyO (organism)

RRID:DGGR_108148

Drosophila melanogaster with name w[*]; Pka-C1[DN]/CyO from DGGR.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01218}attP2 (organism)

RRID:BDSC_31277

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01218}attP2 from BDSC.

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w[1118] (organism)

RRID:BDSC_3605

Drosophila melanogaster with name w[1118] from BDSC.

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w[*]; P{w[+mC]=hs-Ilp2.R}2/CyO, amos[Roi-1] (organism)

RRID:BDSC_37472

Drosophila melanogaster with name w[*]; P{w[+mC]=hs-Ilp2.R}2/CyO, amos[Roi-1] from BDSC.

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w[*]; P{w[+mC]=UAS-myr-Akt1.V}3/TM3, Sb[1] (organism)

RRID:BDSC_50758

Discontinued

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y[1] w[*] P{ry[+t7.2]=hsFLP}12; P{w[+mC]=UAS-Tor.WT}III (organism)

RRID:BDSC_7012

Drosophila melanogaster with name y[1] w[*] P{ry[+t7.2]=hsFLP}12; P{w[+mC]=UAS-Tor.WT}III from BDSC.

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y[1] w[1118]; P{w[+mC]=UAS-InR.A1325D}2 (organism)

RRID:BDSC_8263

Drosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-InR.A1325D}2 from BDSC.

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w[*]; P{w[+mC]=UAS-unc-51.WT}3 (organism)

RRID:BDSC_60734

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-unc-51.WT}3 from BDSC.

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y[1]; P{ry[+t7.2]=neoFRT}42D ptc[S2]/CyO (organism)

RRID:BDSC_6332

Drosophila melanogaster with name y[1]; P{ry[+t7.2]=neoFRT}42D ptc[S2]/CyO from BDSC.

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ptc[tuf-1] Rab32[ltd-1] (organism)

RRID:DGGR_105908

Drosophila melanogaster with name ptc[tuf-1] Rab32[ltd-1] from DGGR.

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P{ry[+t7.2]=hsFLP}1, y[1] w[1118]; P{w[+mC]=UAS-Atg8a.GFP}3 (organism)

RRID:BDSC_51656

Drosophila melanogaster with name P{ry[+t7.2]=hsFLP}1, y[1] w[1118]; P{w[+mC]=UAS-Atg8a.GFP}3 from BDSC.

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Pka-C1[B10] (organism)

RRID:BDSC_32018

Drosophila melanogaster with name Pka-C1[B10] from BDSC.

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w[1118]; P{w[+mC]=UAS-AMPKalpha.T184D}2/CyO (organism)

RRID:BDSC_32110

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-AMPKalpha.T184D}2/CyO from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00923}attP2 (organism)

RRID:BDSC_33966

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00923}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HM04007}attP2 (organism)

RRID:BDSC_31701

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HM04007}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00735}attP2 (organism)

RRID:BDSC_32941

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00735}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01482}attP2 (organism)

RRID:BDSC_31037

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01482}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03872}attP40 (organism)

RRID:BDSC_55686

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMC03872}attP40 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00252}attP2 (organism)

RRID:BDSC_35341

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.GL00252}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01351}attP2 (organism)

RRID:BDSC_34362

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01351}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01804}attP2 (organism)

RRID:BDSC_25794

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01804}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01715}attP2 (organism)

RRID:BDSC_28984

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF01715}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02028}attP40 (organism)

RRID:BDSC_40861

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02028}attP40 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02891}attP2 (organism)

RRID:BDSC_28055

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02891}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02706}attP2 (organism)

RRID:BDSC_27554

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02706}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02897}attP2 (organism)

RRID:BDSC_28060

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02897}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01244}attP2 (organism)

RRID:BDSC_34899

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01244}attP2 from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02786}attP2 (organism)

RRID:BDSC_27706

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02786}attP2 from BDSC.

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Rabbit Anti-phospho Histone H3 (Ser28) Monoclonal Antibody, Unconjugated, Clone E191l (antibody)

RRID:AB_10807285

This monoclonal targets Rabbit phospho Histone H3 (Ser28) Clone E191l

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01358}attP2/TM3, Sb[1] (organism)

RRID:BDSC_34369

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01358}attP2/TM3, Sb[1] from BDSC.

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y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02273}attP2 (organism)

RRID:BDSC_26731

Drosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02273}attP2 from BDSC.

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Cy5-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (antibody)

RRID:AB_2340607

This unknown targets Rabbit IgG (H+L)

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Cy3-AffiniPure Donkey Anti-Rabbit IgG (H+L) (min X Bov,Ck,Gt,GP,Sy Hms,Hrs,Hu,Ms,Rat,Shp Sr Prot) (antibody)

RRID:AB_2307443

This polyclonal targets IgG (H+L)

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Fasciclin III (Drosophila) antibody - Goodman, C.; University of California, Berkeley (antibody)

RRID:AB_528238

This monoclonal targets Fasciclin III (Drosophila)

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Vasa (d-260) (antibody)

RRID:AB_793874

This polyclonal targets Vasa (d-260)

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w[*]; P{w[+mC]=UAS-Rheb.Pa}3 (organism)

RRID:BDSC_9689

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-Rheb.Pa}3 from BDSC.

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w[*]; P{w[+mC]=UAS-ptc.J}B1 (organism)

RRID:BDSC_5817

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-ptc.J}B1 from BDSC.

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w[*]; P{w[+mC]=UAS-ptc.1130X}C (organism)

RRID:BDSC_44612

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-ptc.1130X}C from BDSC.

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w[1118]; P{w[+mC]=UAS-stg.N}16 (organism)

RRID:DGGR_107872

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-stg.N}16 from DGGR.

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