EndoGI modulates Notch signaling and axon guidance in Drosophila.
Signaling through the Notch receptor has dramatically different effects depending on cell type and developmental timing. While a myriad of biological systems affected by Notch have been described, the molecular mechanisms by which a generic Notch signal is translated into a cell-type-specific output are less clear. Canonically, the Notch intracellular domain (NICD) translocates into the nucleus upon ligand binding to transcriptionally regulate target genes. In order to generate specificity, therefore, additional factors must exist that modulate NICD activity. Here we describe a novel regulator of the Notch pathway, Endonuclease GI (EndoGI). EndoGI localizes to the nucleus of most cells and activates Notch signaling when overexpressed. In the absence of endoGI, mutant animals are viable, but uncoordinated as motor neurons fail to innervate their appropriate muscle targets. Our data is therefore consistent with EndoGI functioning as a positive regulator of the Notch signaling pathway, playing a critical role during axon guidance of motor neurons.
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Av., N. Seattle, WA 98109, USA.
David D
DD
O'Keefe
Bruce A
BA
Edgar
Leslie J
LJ
Saucedo
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D004625:Embryo, Nonmammalian / Q000378:metabolism / Q000473:pathology; D005123:Eye / Q000254:growth & development / Q000648:ultrastructure; D005260:Female; D017344:Genes, Insect / Q000235:genetics; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D021381:Protein Transport; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction
D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C558783:endonuclease G inhibitor, Drosophila