title: miR-216a regulates snx5, a novel notch signaling pathway component, during zebrafish retinal development.
abstract: Precise regulation of Notch signaling is essential for normal vertebrate development. Mind bomb (Mib) is a ubiquitin ligase that is required for activation of Notch by Notch׳s ligand, Delta. Sorting Nexin 5 (SNX5) co-localizes with Mib and Delta complexes and has been shown to directly bind to Mib. We show that microRNA-216a (miR-216a) is expressed in the retina during early development and regulates snx5 to precisely regulate Notch signaling. miR-216a and snx5 have complementary expression patterns. Knocking down miR-216a and/or overexpression of snx5 resulted in increased Notch activation. Conversely, knocking down snx5 and/or miR-216a overexpression caused a decrease in Notch activation. We propose a model in which SNX5, precisely controlled by miR-216a, is a vital partner of Mib in promoting endocytosis of Delta and subsequent activation of Notch signaling.
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN.
authors: Abigail F
authors: AF
authors: Olena
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN.
authors: Mahesh B
authors: MB
authors: Rao
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN.
authors: Elizabeth J
authors: EJ
authors: Thatcher
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN.
authors: Shu-Yu
authors: SY
authors: Wu
authors: Department of Biological Sciences, Vanderbilt University, Nashville, TN.
authors: James G
authors: JG
authors: Patton
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D007091:Image Processing, Computer-Assisted; D015151:Immunoblotting; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D008954:Models, Biological; D051880:Receptors, Notch / Q000378:metabolism; D012160:Retina / Q000196:embryology* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D058305:Sorting Nexins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C000597779:MIRN216 microRNA, zebrafish; D008565:Membrane Proteins; D035683:MicroRNAs; D051880:Receptors, Notch; C513495:Snx5 protein, zebrafish; D058305:Sorting Nexins; D029961:Zebrafish Proteins; C064045:delta protein; D044767:Ubiquitin-Protein Ligases; C471932:mib1 protein, zebrafish
keywords: Notch signaling; Retina; Sorting Nexin 5; Zebrafish; miR-216a; microRNA
references: Nat Rev Genet. 2004 Jul;5(7):522-31
references: 15211354
references: Development. 1999 May;126(9):1811-21
references: 10101116
references: Nat Protoc. 2008;3(1):59-69
references: 18193022
references: FEBS Lett. 2005 Oct 31;579(26):5911-22
references: 16111679
references: Mech Dev. 2009 Oct;126(10):898-912
references: 19595765
references: Genome Biol. 2007;8(8):R173
references: 17711588
references: Development. 2001 Apr;128(7):1099-107
references: 11245575
references: Science. 2005 Jul 8;309(5732):310-1
references: 15919954
references: Methods Cell Biol. 1999;60:43-70
references: 9891330
references: Nat Cell Biol. 2012 Jan;14(1):29-37
references: 22193161
references: Cell. 2005 Jan 14;120(1):15-20
references: 15652477
references: Hum Mol Genet. 2012 Jul 1;21(13):2991-3000
references: 22498974
references: Dev Biol. 2007 Jan 15;301(2):555-67
references: 17134690
references: Development. 2000 Apr;127(7):1373-85
references: 10704384
references: Dev Cell. 2012 May 15;22(5):1052-64
references: 22595676
references: Dev Dyn. 1995 Jul;203(3):253-310
references: 8589427
references: Neural Dev. 2010;5:25
references: 20920300
references: Development. 2012 Dec 1;139(23):4356-64
references: 23132244
references: FEBS Lett. 2006 Aug 7;580(18):4409-16
references: 16857196
references: Science. 2012 Apr 13;336(6078):233-7
references: 22422859
references: Science. 2005 May 6;308(5723):833-8
references: 15774722
references: Dev Cell. 2009 May;16(5):633-47
references: 19460341
references: Dev Biol. 2005 Feb 15;278(2):381-95
references: 15680358
references: Dev Dyn. 2007 Aug;236(8):2172-80
references: 17584857
references: Development. 2001 Oct;128(19):3675-83
references: 11585794
references: Annu Rev Biochem. 2010;79:351-79
references: 20533884
references: Nat Rev Genet. 2011 Feb;12(2):99-110
references: 21245828
references: Results Probl Cell Differ. 2002;40:346-70
references: 12353485
references: Dev Biol. 2011 Feb 15;350(2):279-89
references: 21145318
references: Cell. 1993 Dec 3;75(5):843-54
references: 8252621
references: Development. 2009 Jan;136(2):197-206
references: 19056830
references: Genes Dev. 1994 Jun 1;8(11):1311-23
references: 7926732
references: Zebrafish. 2004;1(3):257-71
references: 18248236
references: Development. 2011 May;138(9):1737-45
references: 21447549
references: Cell. 2004 Jan 23;116(2):281-97
references: 14744438
references: Development. 2011 May;138(9):1817-26
references: 21447552
references: Nat Rev Mol Cell Biol. 2008 Jul;9(7):574-82
references: 18523436
references: Gene Expr Patterns. 2006 Oct;6(8):1007-13
references: 16765104
references: Cell. 1993 Dec 3;75(5):855-62
references: 8252622
references: Nat Cell Biol. 2011 Aug;13(8):914-23
references: 21725319
references: Nucleic Acids Res. 2008 Aug;36(13):4277-85
references: 18583362
references: Nat Genet. 2007 Feb;39(2):259-63
references: 17220889
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D154-8
references: 17991681
references: Science. 2012 Apr 13;336(6078):237-40
references: 22499947
references: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14385-9
references: 16983084
references: Nat Rev Neurosci. 2006 Feb;7(2):93-102
references: 16429119
references: Science. 2006 Apr 7;312(5770):75-9
references: 16484454
references: Dev Cell. 2003 Jan;4(1):67-82
references: 12530964
references: Dev Biol. 2007 Apr 15;304(2):735-44
references: 17306248
references: J Cell Biol. 2012 Apr 16;197(2):219-30
references: 22492727
references: Mol Cell. 2012 May 25;46(4):507-17
references: 22503104
references: PLoS One. 2013;8(2):e57080
references: 23451149
references: J Cell Biol. 2009 Apr 6;185(1):115-27
references: 19332888
references: Biol Open. 2012 Jun 15;1(6):566-9
references: 23213449
references: Development. 2011 Jul;138(14):2947-56
references: 21653612
references: Genes Dev. 2009 Mar 1;23(5):619-32
references: 19240126
references: PLoS Biol. 2005 Aug;3(8):e254
references: 16089502