title: The microRNA pathway regulates the temporal pattern of Notch signaling in Drosophila follicle cells.
abstract: Multicellular development requires the correct spatial and temporal regulation of cell division and differentiation. These processes are frequently coordinated by the activities of various signaling pathways such as Notch signaling. From a screen for modifiers of Notch signaling in Drosophila we have identified the RNA helicase Belle, a recently described component of the RNA interference pathway, as an important regulator of the timing of Notch activity in follicle cells. We found that loss of Belle delays activation of Notch signaling, which results in delayed follicle cell differentiation and defects in the cell cycle. Because mutations in well-characterized microRNA components phenocopied the Notch defects observed in belle mutants, Belle might be functioning in the microRNA pathway in follicle cells. The effect of loss of microRNAs on Notch signaling occurs upstream of Notch cleavage, as expression of the constitutively active intracellular domain of Notch in microRNA-defective cells restored proper activation of Notch. Furthermore, we present evidence that the Notch ligand Delta is an important target of microRNA regulation in follicle cells and regulates the timing of Notch activation through cis inhibition of Notch. Here we have uncovered a complex regulatory process in which the microRNA pathway promotes Notch activation by repressing Delta-mediated inhibition of Notch in follicle cells.
authors: Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
authors: John S
authors: JS
authors: Poulton
authors: Yi-Chun
authors: YC
authors: Huang
authors: Laila
authors: L
authors: Smith
authors: Jianjun
authors: J
authors: Sun
authors: Nicholas
authors: N
authors: Leake
authors: Justin
authors: J
authors: Schleede
authors: Leslie M
authors: LM
authors: Stevens
authors: Wu-Min
authors: WM
authors: Deng
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D015536:Down-Regulation / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics* / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology / Q000196:embryology / Q000378:metabolism* / Q000502:physiology*; D020365:RNA Helicases / Q000235:genetics / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C497759:N protein, Drosophila; D051880:Receptors, Notch; D012097:Repressor Proteins; C064045:delta protein; C558829:Bel protein, Drosophila; D020365:RNA Helicases