Inactivation of the Huntington's disease gene (Hdh) impairs anterior streak formation and early patterning of the mouse embryo |
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Authors: | Woda Juliana M Calzonetti Teresa Hilditch-Maguire Paige Duyao Mabel P Conlon Ronald A MacDonald Marcy E |
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Institution: | 1. Department of Microbiology and Molecular Genetics, The University of Vermont, 05405, 322 Stafford Hall, 95 Carrigan Drive, Burlington, VT, USA 2. Rollins School of Public Health, Emory University, 30322, Atlanta, GA, USA 3. Faculte de Medecine Lariboisiere, INSERM E365, 10 avenue de Verdun, 75010, Paris, France 4. College of Veterinary Medicine, Kansas State University, Manhattan, 66506, KS, USA 5. Department of Civil Engineering, The University of Minnesota, Minneapolis, 55455, MN, USA
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Abstract: | Background Delta, Notch, and Scabrous often function together to make different cell types and refine tissue patterns during Drosophila development. Delta is known as the ligand that triggers Notch receptor activity. Scabrous is known to bind Notch and promote Notch activity in response to Delta. It is not known if Scabrous binds Delta or Delta has activity other than its activity as a ligand of Notch. It is very difficult to clearly determine this binding or activity in vivo as all Notch, Delta, and Scabrous activities are required simultaneously or successively in an inter-dependent manner. Results Using Drosophila cultured cells we show that the full length Delta promotes accumulation of Daughterless protein, fringe RNA, and pangolin RNA in the absence of Scabrous or Notch. Scabrous binds Delta and suppresses this activity even though it increases the level of the Delta intracellular domain. We also show that Scabrous can promote Notch receptor activity, in the absence of Delta. Conclusion Delta has activity that is independent of its activity as a ligand of Notch. Scabrous suppresses this Delta activity. Scabrous also promotes Notch activity that is dependent on Delta's ligand activity. Thus, Notch, Delta, and Scabrous might function in complex combinatorial or mutually exclusive interactions during development. The data reported here will be of significant help in understanding these interactions in vivo. |
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