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Ral GTPases are RAS effector molecules and by implication a potential therapeutic target for RAS mutant cancer. However, very little is known about their roles in stem cells and tissue homeostasis. Using Drosophila, we identified expression of RalA in intestinal stem cells (ISCs) and progenitor cells of the fly midgut. RalA was required within ISCs for efficient regeneration downstream of Wnt signaling. Within the murine intestine, genetic deletion of either mammalian ortholog, Rala or Ralb, reduced ISC function and Lgr5 positivity, drove hypersensitivity to Wnt inhibition, and impaired tissue regeneration following damage. Ablation of both genes resulted in rapid crypt death. Mechanistically, RALA and RALB were required for efficient internalization of the Wnt receptor Frizzled-7. Together, we identify a conserved role for RAL GTPases in the promotion of optimal Wnt signaling, which defines ISC number and regenerative potential.
Pubmed ID: 30853556 RIS Download
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View all literature mentionsInstrument for cell sorting by BD Biosciences where positive air pressure forces sample cell through an optically gel-coupled cuvette . Hydrodynamic focusing guides particles in a single-file stream through the cuvette, where laser light intercepts the stream at the sample interrogation point.Fluorescence activated cell sorting instrument. Flow cytometer as high speed fixed alignment benchtop cell sorter. Enables multicolor analysis of up to 13 fluorescent markers and two scatter parameters at time.
View all literature mentionsSoftware 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.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsThis unknown targets β-Galactosidase
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis polyclonal targets Human RIP1
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis polyclonal targets Cleaved Notch1 (Val1744)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets RalB
View all literature mentionsThis monoclonal targets Ral A
View all literature mentionsThis polyclonal targets Fzd7
View all literature mentionsThis polyclonal targets Frizzled-5
View all literature mentionsThis polyclonal targets Frizzled 7
View all literature mentionsThis polyclonal secondary targets Guinea Pig IgG (H+L)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis unknown targets Chicken IgG (H+L)
View all literature mentionsThis monoclonal targets Mouse Drosophila Wingless protein
View all literature mentionsThis polyclonal targets DsRed
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets Phospho-Histone H3 (Ser10)
View all literature mentionsThis monoclonal targets Mouse Drosophila Armadillo Protein
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{KK108857}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF03259}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-wg.H.T:HA1}6C from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{GD8562}v43622 from Flybase.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-RedStinger}4/CyO from BDSC.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{PT-GFSTF.1}Dl[MI04868-GFSTF.1]/TM6C, Sb[1] Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mW.hs]=en2.4-GAL4}e16E from BDSC.
View all literature mentionsDrosophila melanogaster with name P{KK101635}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name P{KK108989}VIE-260B from Flybase.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsStatistical 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.
View all literature mentionsA software used to control and operate the Applied Biosystems 7500 Real-Time PCR system.
View all literature mentionsUser interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.
View all literature mentionsNeuronJ is an ImageJ plugin to facilitate the tracing and quantification of elongated structures in two-dimensional (2D) images (8-bit gray-scale and indexed color), in particular neurites in fluorescence microscopy images. Sponsors: The development of NeuronJ started while the primary developer ( Dr. Erik Meijering, PhD) was with the Biomedical Imaging Group (collaborating with people from the Laboratory of Cellular Neurobiology) of the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland, and was finished while Dr. Meijering was with the Biomedical Imaging Group Rotterdam in the Netherlands.
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsThis polyclonal targets Phospho-Histone H3 (Ser10)
View all literature mentionsThis polyclonal targets DsRed
View all literature mentionsThis monoclonal targets Mouse Drosophila Wingless protein
View all literature mentionsThis unknown targets β-Galactosidase
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsThis unknown targets β-Galactosidase
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-wg.H.T:HA1}6C from BDSC.
View all literature mentionsDrosophila melanogaster with name P{KK108857}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{GD8562}v43622 from Flybase.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF03259}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name P{KK108989}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name P{KK101635}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mW.hs]=en2.4-GAL4}e16E from BDSC.
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{PT-GFSTF.1}Dl[MI04868-GFSTF.1]/TM6C, Sb[1] Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-RedStinger}4/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsThis unknown targets Chicken IgG (H+L)
View all literature mentionsStatistical 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.
View all literature mentionsA software used to control and operate the Applied Biosystems 7500 Real-Time PCR system.
View all literature mentionsUser interface software for Carl Zeiss light microscopy imaging systems. ZEN is the universal user interface you will see on every imaging system from ZEISS. After selecting fluorophore, ZEN applies the necessary settings to collect and organize data.
View all literature mentionsNeuronJ is an ImageJ plugin to facilitate the tracing and quantification of elongated structures in two-dimensional (2D) images (8-bit gray-scale and indexed color), in particular neurites in fluorescence microscopy images. Sponsors: The development of NeuronJ started while the primary developer ( Dr. Erik Meijering, PhD) was with the Biomedical Imaging Group (collaborating with people from the Laboratory of Cellular Neurobiology) of the Swiss Federal Institute of Technology in Lausanne (EPFL), Switzerland, and was finished while Dr. Meijering was with the Biomedical Imaging Group Rotterdam in the Netherlands.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-mCD8::GFP.L}LL5, P{UAS-mCD8::GFP.L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-wg.H.T:HA1}6C from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF03259}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mW.hs]=en2.4-GAL4}e16E from BDSC.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsAllele Detail: Targeted This is a legacy resource.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; Mi{PT-GFSTF.1}Dl[MI04868-GFSTF.1]/TM6C, Sb[1] Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-RedStinger}4/CyO from BDSC.
View all literature mentionsThis unknown targets Guinea Pig IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal secondary targets Guinea Pig IgG (H+L)
View all literature mentionsThis polyclonal targets Frizzled-5
View all literature mentionsThis polyclonal targets Fzd7
View all literature mentionsThis polyclonal targets Frizzled 7
View all literature mentionsDrosophila melanogaster with name P{KK108857}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{GD8562}v43622 from Flybase.
View all literature mentionsDrosophila melanogaster with name P{KK108989}VIE-260B from Flybase.
View all literature mentionsDrosophila melanogaster with name P{KK101635}VIE-260B from Flybase.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets Cleaved Notch1 (Val1744)
View all literature mentionsThis monoclonal targets Catenin, beta
View all literature mentionsThis polyclonal targets Cleaved Caspase-3 (Asp175)
View all literature mentionsThis polyclonal targets RFP
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis polyclonal targets Human RIP1
View all literature mentionsThis monoclonal targets RalB
View all literature mentionsThis monoclonal targets Ral A
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsThis monoclonal targets Mouse Drosophila Armadillo Protein
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