title: Overlapping functions of microRNAs in control of apoptosis during Drosophila embryogenesis.
abstract: Regulation of apoptosis is crucial for tissue homeostasis under normal development and environmental stress. In Drosophila, cell death occurs in different developmental processes including embryogenesis. Here, we report that two members of the miR-2 seed family of microRNAs, miR-6 and miR-11, function together to limit the level of apoptosis during Drosophila embryonic development. Mutants lacking both miR-6 and miR-11 show embryonic lethality and defects in the central nervous system (CNS). We provide evidence that miR-6/11 functions through regulation of the proapoptotic genes, reaper (rpr), head involution defective (hid), grim and sickle (skl). Upregulation of these proapoptotic genes is responsible for the elevated apoptosis and the CNS defects in the mutants. These findings demonstrate that the activity of the proapoptotic genes is kept in check by miR-6/11 to ensure normal development.
authors.affiliation: Institute of Molecular Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
authors.forename: W
authors.initials: W
authors.lastname: Ge
authors.forename: Y-W
authors.initials: YW
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Weng
authors.forename: S F
authors.initials: SF
authors.lastname: Lim
authors.forename: M
authors.initials: M
authors.lastname: Buescher
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: S M
authors.initials: SM
authors.lastname: Cohen
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002490:Central Nervous System / Q000196:embryology / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C108880:HID protein, Drosophila; D035683:MicroRNAs; D009479:Neuropeptides; C108881:grim protein, Drosophila; C086973:rpr protein, Drosophila; C452430:skl protein, Drosophila
references.citation: Genetics. 2006 Jun;173(2):769-77
references.pmid: 16547094
references.citation: Cell Death Differ. 2010 Feb;17(2):193-9
references.pmid: 19461653
references.citation: J Cell Sci. 2005 May 1;118(Pt 9):1779-87
references.pmid: 15860727
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: Genes Dev. 2009 May 1;23(9):1046-51
references.pmid: 19372388
references.citation: Cancer Res. 2010 Oct 15;70(20):8108-16
references.pmid: 20813833
references.citation: Cell Death Differ. 1998 Nov;5(11):930-9
references.pmid: 9846179
references.citation: Development. 1991 Nov;113(3):825-39
references.pmid: 1821853
references.citation: Genetics. 2009 Sep;183(1):399-402
references.pmid: 19564483
references.citation: Neuron. 1998 Nov;21(5):991-1001
references.pmid: 9856456
references.citation: Nature. 2001 Sep 20;413(6853):311-6
references.pmid: 11565033
references.citation: Curr Biol. 2004 Jun 8;14(11):965-74
references.pmid: 15182669
references.citation: PLoS Biol. 2003 Dec;1(3):E60
references.pmid: 14691535
references.citation: Mech Dev. 2004 Dec;121(12):1523-30
references.pmid: 15511643
references.citation: Nat Rev Cancer. 2002 Oct;2(10):764-76
references.pmid: 12360279
references.citation: Dev Cell. 2002 Feb;2(2):159-70
references.pmid: 11832242
references.citation: Cell. 2003 Apr 4;113(1):25-36
references.pmid: 12679032
references.citation: Cell. 2006 Aug 25;126(4):767-74
references.pmid: 16923395
references.citation: Proc Natl Acad Sci U S A. 1997 May 13;94(10):5131-6
references.pmid: 9144202
references.citation: Genes Dev. 1995 Jun 15;9(12):1445-55
references.pmid: 7601349
references.citation: Cell. 1991 Feb 22;64(4):801-15
references.pmid: 1997208
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 21;106(29):12085-90
references.pmid: 19597153
references.citation: Development. 2004 May;131(10):2409-18
references.pmid: 15128670
references.citation: Blood. 2007 Aug 15;110(4):1330-3
references.pmid: 17496199
references.citation: Cell. 2000 Mar 31;101(1):103-13
references.pmid: 10778860
references.citation: Curr Biol. 2008 Apr 8;18(7):501-6
references.pmid: 18394895
references.citation: Neurosci Lett. 1988 Feb 29;85(2):169-71
references.pmid: 3374833
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2556-61
references.pmid: 12589026
references.citation: PLoS Biol. 2010 Jun 15;8(6):e1000396
references.pmid: 20563308
references.citation: Curr Biol. 2006 Jul 25;16(14):1453-8
references.pmid: 16860746
references.citation: Cell. 2005 Jul 1;121(7):1097-108
references.pmid: 15989958
references.citation: Genome Res. 2007 Dec;17(12):1850-64
references.pmid: 17989254
references.citation: Development. 2002 Mar;129(6):1467-76
references.pmid: 11880355
references.citation: Cell. 1996 Nov 15;87(4):651-60
references.pmid: 8929534
references.citation: PLoS Biol. 2005 Mar;3(3):e85
references.pmid: 15723116
references.citation: Genes Dev. 2011 Sep 1;25(17):1820-34
references.pmid: 21856777
references.citation: Cell. 2005 Aug 12;122(3):421-34
references.pmid: 16096061
references.citation: Cell. 2001 Mar 23;104(6):805-8
references.pmid: 11290317
references.citation: Nature. 2008 Jun 5;453(7196):798-802
references.pmid: 18463631
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 27;104(9):3312-7
references.pmid: 17360644
references.citation: Dev Cell. 2003 Apr;4(4):599-605
references.pmid: 12689597
references.citation: Cell. 1998 Oct 30;95(3):331-41
references.pmid: 9814704
references.citation: Mol Cell. 2000 Mar;5(3):445-55
references.pmid: 10882130
references.citation: Cell. 2005 Dec 16;123(6):1133-46
references.pmid: 16337999
references.citation: Cell. 1998 Oct 30;95(3):319-29
references.pmid: 9814703
references.citation: Methods Mol Biol. 2011;732:99-120
references.pmid: 21431708