title: Blimp1 suppresses Chx10 expression in differentiating retinal photoreceptor precursors to ensure proper photoreceptor development.
abstract: The zinc finger transcription factor Blimp1 plays fundamentally important roles in many cell lineages and in the early development of several cell types, including B and T lymphocytes and germ cells. Although Blimp1 expression in developing retinal photoreceptor cells has been reported, its function remains unclear. We identified Blimp1 as a downstream factor of Otx2, which plays an essential role in photoreceptor cell fate determination. To investigate Blimp1 function in the mouse retina, we ablated Blimp1 in the developing retina by conditional gene targeting. In the Blimp1 conditional knockout (CKO) retina, the number of photoreceptor cells was markedly reduced in the differentiated retina. We found that the numbers of both bipolar-like cells and proliferating retinal cells increased noticeably, with ectopic localizations in the postnatal developing retina. In contrast, a reduction of the number of photoreceptor precursors was observed during development. Forced expression of Blimp1 by in vivo electroporation suppressed bipolar cell genesis in the developing retina. Multiple genes involved in bipolar development, including Chx10, were upregulated in the Blimp1 CKO retina. Furthermore, we showed that Blimp1 can bind to the Chx10 enhancer and repress Chx10 enhancer activity. These results suggest that Blimp1 plays a crucial role in photoreceptor development by repressing genes involved in bipolar cell fate specification and retinal cell proliferation in differentiating photoreceptor precursors.
authors.affiliation: Department of Developmental Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Katoh
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Omori
authors.forename: Akishi
authors.initials: A
authors.lastname: Onishi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Sato
authors.forename: Mineo
authors.initials: M
authors.lastname: Kondo
authors.forename: Takahisa
authors.initials: T
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D018274:Electroporation; D018507:Gene Expression Regulation, Developmental; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D020411:Oligonucleotide Array Sequence Analysis; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000196:embryology / Q000254:growth & development* / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000502:physiology; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C513258:Prdm1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors; C088975:Vsx2 protein, mouse; D000074462:Positive Regulatory Domain I-Binding Factor 1
references.citation: J Neurosci. 2008 Jul 30;28(31):7748-64
references.pmid: 18667607
references.citation: Science. 1997 Apr 25;276(5312):596-9
references.pmid: 9110979
references.citation: J Immunol. 2004 Nov 1;173(9):5556-63
references.pmid: 15494505
references.citation: Development. 2005 Mar;132(6):1315-25
references.pmid: 15750184
references.citation: Mol Cell Biol. 2000 Apr;20(7):2592-603
references.pmid: 10713181
references.citation: Dev Biol. 2004 Jul 15;271(2):388-402
references.pmid: 15223342
references.citation: Genes Dev. 1994 Jun 1;8(11):1300-10
references.pmid: 7986270
references.citation: J Neurosci. 2002 Mar 1;22(5):1640-7
references.pmid: 11880494
references.citation: Neurosci Lett. 2003 Dec 15;353(1):29-32
references.pmid: 14642430
references.citation: Cell. 2006 Aug 11;126(3):597-609
references.pmid: 16901790
references.citation: Nat Genet. 1999 Dec;23(4):466-70
references.pmid: 10581037
references.citation: Mol Cell Biol. 2007 Dec;27(23):8318-29
references.pmid: 17908793
references.citation: Cell. 1997 Nov 14;91(4):531-41
references.pmid: 9390562
references.citation: Dev Biol. 2005 May 15;281(2):240-55
references.pmid: 15893976
references.citation: Oncogene. 2001 Oct 25;20(48):7073-84
references.pmid: 11704831
references.citation: BMC Dev Biol. 2008 Oct 14;8:101
references.pmid: 18854032
references.citation: Mech Dev. 2002 Sep;117(1-2):305-9
references.pmid: 12204275
references.citation: Development. 2010 Feb;137(4):619-29
references.pmid: 20110327
references.citation: Genesis. 2007 Aug;45(8):502-7
references.pmid: 17661397
references.citation: Mol Cell Biol. 2000 Dec;20(23):8684-95
references.pmid: 11073970
references.citation: Nat Cell Biol. 2006 Jun;8(6):623-30
references.pmid: 16699504
references.citation: Cell. 1994 Apr 22;77(2):297-306
references.pmid: 8168136
references.citation: Cell. 2007 Oct 19;131(2):378-90
references.pmid: 17956737
references.citation: Nat Genet. 1996 Apr;12(4):376-84
references.pmid: 8630490
references.citation: Curr Opin Neurobiol. 1996 Aug;6(4):542-6
references.pmid: 8794108
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4988-93
references.pmid: 16547132
references.citation: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):16-22
references.pmid: 14603031
references.citation: Nat Immunol. 2006 May;7(5):466-74
references.pmid: 16565720
references.citation: J Comp Neurol. 1979 Nov 15;188(2):245-62
references.pmid: 500858
references.citation: Acta Neuropathol. 1997 Jul;94(1):6-15
references.pmid: 9224524
references.citation: Vis Neurosci. 2005 Sep-Oct;22(5):575-86
references.pmid: 16332268
references.citation: Nucleic Acids Res. 2001 May 15;29(10):2154-62
references.pmid: 11353085
references.citation: Curr Biol. 2004 Oct 5;14(19):1772-7
references.pmid: 15458650
references.citation: Reproduction. 2008 Oct;136(4):503-14
references.pmid: 18583473
references.citation: J Cell Biol. 1996 Feb;132(3):413-25
references.pmid: 8636218
references.citation: Nat Genet. 2000 Aug;25(4):397-401
references.pmid: 10932181
references.citation: Nat Neurosci. 2003 Dec;6(12):1255-63
references.pmid: 14625556
references.citation: Curr Eye Res. 2008 Jan;33(1):91-9
references.pmid: 18214746
references.citation: Mol Cell Biol. 2009 Mar;29(6):1421-31
references.pmid: 19124609
references.citation: Curr Opin Immunol. 2007 Apr;19(2):156-62
references.pmid: 17291741
references.citation: Nat Rev Immunol. 2005 Mar;5(3):230-42
references.pmid: 15738953
references.citation: Immunity. 2002 Jul;17(1):51-62
references.pmid: 12150891
references.citation: Development. 2005 Jan;132(2):393-404
references.pmid: 15623803
references.citation: J Neuropathol Exp Neurol. 2003 Jan;62(1):68-74
references.pmid: 12528819
references.citation: PLoS One. 2007 Jul 25;2(7):e643
references.pmid: 17653270
references.citation: PLoS One. 2008 Feb 13;3(2):e1588
references.pmid: 18270576
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):589-95
references.pmid: 8570600
references.citation: Nature. 2005 Jul 14;436(7048):207-13
references.pmid: 15937476
references.citation: Immunity. 2003 Oct;19(4):607-20
references.pmid: 14563324
references.citation: Genes Dev. 1999 Jan 1;13(1):125-37
references.pmid: 9887105
references.citation: Genes Dev. 1991 May;5(5):868-79
references.pmid: 1851123
references.citation: Nat Immunol. 2006 May;7(5):457-65
references.pmid: 16565721
references.citation: Nat Immunol. 2004 Mar;5(3):299-308
references.pmid: 14985713