Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Bcl6a function is required during optic cup formation to prevent p53-dependent apoptosis and colobomata.
Lee J, Lee BK, Gross JM.
???displayArticle.abstract???
Mutations in BCOR (Bcl6 corepressor) are found in patients with oculo-facio-cardio-dental (OFCD) syndrome, a congenital disorder affecting visual system development, and loss-of-function studies in zebrafish and Xenopus demonstrate a role for Bcor during normal optic cup development in preventing colobomata. The mechanism whereby BCOR functions during eye development to prevent colobomata is not known, but in other contexts it serves as a transcriptional corepressor that potentiates transcriptional repression by B cell leukemia/lymphoma 6 (BCL6). Here, we have explored the function of the zebrafish ortholog of Bcl6, Bcl6a, during eye development, and our results demonstrate that Bcl6a, like Bcor, is required to prevent colobomata during optic cup formation. Our data demonstrate that Bcl6a acts downstream of Vax1 and Vax2, known regulators of ventral optic cup formation and choroid fissure closure, and that bcl6a is a direct target of Vax2. Together, this regulatory network functions to repress p53 expression and thereby suppress apoptosis in the developing optic cup. Furthermore, our data demonstrate that Bcl6a functions cooperatively with Bcor, Rnf2 and Hdac1 in a common gene regulatory network that acts to repress p53 and prevent colobomata. Together, these data support a model in which p53-dependent apoptosis needs to be tightly regulated for normal optic cup formation and that Bcl6a, Bcor, Rnf2 and Hdac1 activities mediate this regulation.
Albagli-Curiel,
Ambivalent role of BCL6 in cell survival and transformation.
2003, Pubmed
Albagli-Curiel,
Ambivalent role of BCL6 in cell survival and transformation.
2003,
Pubmed Bajalica-Lagercrantz,
Expression of the BCL6 gene in the pre- and postnatal mouse.
1998,
Pubmed Bannister,
Spatial distribution of di- and tri-methyl lysine 36 of histone H3 at active genes.
2005,
Pubmed Barbieri,
Vax2 inactivation in mouse determines alteration of the eye dorsal-ventral axis, misrouting of the optic fibres and eye coloboma.
2002,
Pubmed
,
Xenbase Barbieri,
A homeobox gene, vax2, controls the patterning of the eye dorsoventral axis.
1999,
Pubmed
,
Xenbase Barlev,
Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases.
2001,
Pubmed Baron,
Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas.
1993,
Pubmed Baron,
The human programmed cell death-2 (PDCD2) gene is a target of BCL6 repression: implications for a role of BCL6 in the down-regulation of apoptosis.
2002,
Pubmed Bereshchenko,
Acetylation inactivates the transcriptional repressor BCL6.
2002,
Pubmed Bertuzzi,
The homeodomain protein vax1 is required for axon guidance and major tract formation in the developing forebrain.
1999,
Pubmed Bibliowicz,
Toward a better understanding of human eye disease insights from the zebrafish, Danio rerio.
2011,
Pubmed Biehlmaier,
Onset and time course of apoptosis in the developing zebrafish retina.
2001,
Pubmed Blythe,
Chromatin immunoprecipitation in early Xenopus laevis embryos.
2009,
Pubmed
,
Xenbase Brown,
Expression profiling during ocular development identifies 2 Nlz genes with a critical role in optic fissure closure.
2009,
Pubmed Chang,
BCL-6, a POZ/zinc-finger protein, is a sequence-specific transcriptional repressor.
1996,
Pubmed Chang,
Uveal coloboma: clinical and basic science update.
2006,
Pubmed Cole,
Apoptosis in the developing zebrafish embryo.
2001,
Pubmed Dale,
Fate map for the 32-cell stage of Xenopus laevis.
1987,
Pubmed
,
Xenbase Dent,
Control of inflammation, cytokine expression, and germinal center formation by BCL-6.
1997,
Pubmed Dhordain,
The LAZ3(BCL-6) oncoprotein recruits a SMRT/mSIN3A/histone deacetylase containing complex to mediate transcriptional repression.
1998,
Pubmed Dhordain,
Corepressor SMRT binds the BTB/POZ repressing domain of the LAZ3/BCL6 oncoprotein.
1997,
Pubmed Draper,
Inhibition of zebrafish fgf8 pre-mRNA splicing with morpholino oligos: a quantifiable method for gene knockdown.
2001,
Pubmed
,
Xenbase Erdmann,
N-cadherin is essential for retinal lamination in the zebrafish.
2003,
Pubmed Fitzpatrick,
Developmental eye disorders.
2005,
Pubmed Fukuda,
Fbxl10/Kdm2b deficiency accelerates neural progenitor cell death and leads to exencephaly.
2011,
Pubmed Funatsu,
Gene expression analysis of the late embryonic mouse cerebral cortex using DNA microarray: identification of several region- and layer-specific genes.
2004,
Pubmed Gearhart,
Polycomb group and SCF ubiquitin ligases are found in a novel BCOR complex that is recruited to BCL6 targets.
2006,
Pubmed Gestri,
Reduced TFAP2A function causes variable optic fissure closure and retinal defects and sensitizes eye development to mutations in other morphogenetic regulators.
2009,
Pubmed Goldsmith,
The zebrafish as a tool for understanding the biology of visual disorders.
2003,
Pubmed Gorlin,
Oculo-facio-cardio-dental (OFCD) syndrome.
1996,
Pubmed Gregory-Evans,
SNP genome scanning localizes oto-dental syndrome to chromosome 11q13 and microdeletions at this locus implicate FGF3 in dental and inner-ear disease and FADD in ocular coloboma.
2007,
Pubmed Gregory-Evans,
Ocular coloboma: a reassessment in the age of molecular neuroscience.
2004,
Pubmed Gross,
Zebrafish mutants as models for congenital ocular disorders in humans.
2008,
Pubmed Hallonet,
Vax1 is a novel homeobox-containing gene expressed in the developing anterior ventral forebrain.
1998,
Pubmed
,
Xenbase Hallonet,
Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system.
1999,
Pubmed
,
Xenbase Havis,
Whole embryo chromatin immunoprecipitation protocol for the in vivo study of zebrafish development.
2006,
Pubmed Hedera,
Oculo-facio-cardio-dental syndrome: skewed X chromosome inactivation in mother and daughter suggest X-linked dominant Inheritance.
2003,
Pubmed Heisenberg,
Zebrafish aussicht mutant embryos exhibit widespread overexpression of ace (fgf8) and coincident defects in CNS development.
1999,
Pubmed Hilton,
Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination.
2007,
Pubmed
,
Xenbase Hornby,
Regional variation in blindness in children due to microphthalmos, anophthalmos and coloboma.
2000,
Pubmed Huynh,
BCoR, a novel corepressor involved in BCL-6 repression.
2000,
Pubmed Jowett,
Whole-mount in situ hybridizations on zebrafish embryos using a mixture of digoxigenin- and fluorescein-labelled probes.
1994,
Pubmed Kerckaert,
LAZ3, a novel zinc-finger encoding gene, is disrupted by recurring chromosome 3q27 translocations in human lymphomas.
1993,
Pubmed Kim,
Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression.
2007,
Pubmed Kojima,
Testicular germ cell apoptosis in Bcl6-deficient mice.
2001,
Pubmed Langheinrich,
Zebrafish as a model organism for the identification and characterization of drugs and genes affecting p53 signaling.
2002,
Pubmed Leamey,
Differential gene expression between sensory neocortical areas: potential roles for Ten_m3 and Bcl6 in patterning visual and somatosensory pathways.
2008,
Pubmed Lee,
Zebrafish blowout provides genetic evidence for Patched1-mediated negative regulation of Hedgehog signaling within the proximal optic vesicle of the vertebrate eye.
2008,
Pubmed Lee,
Laminin beta1 and gamma1 containing laminins are essential for basement membrane integrity in the zebrafish eye.
2007,
Pubmed Li,
Olig1 and Sox10 interact synergistically to drive myelin basic protein transcription in oligodendrocytes.
2007,
Pubmed Livak,
Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.
2001,
Pubmed Logarajah,
BCL-6 is expressed in breast cancer and prevents mammary epithelial differentiation.
2003,
Pubmed Macdonald,
The Pax protein Noi is required for commissural axon pathway formation in the rostral forebrain.
1997,
Pubmed Malicki,
Zebrafish N-cadherin, encoded by the glass onion locus, plays an essential role in retinal patterning.
2003,
Pubmed Masai,
N-cadherin mediates retinal lamination, maintenance of forebrain compartments and patterning of retinal neurites.
2003,
Pubmed Mui,
The homeodomain protein Vax2 patterns the dorsoventral and nasotemporal axes of the eye.
2002,
Pubmed Nadauld,
Dual roles for adenomatous polyposis coli in regulating retinoic acid biosynthesis and Wnt during ocular development.
2006,
Pubmed Nakayama,
Fgf19 is required for zebrafish lens and retina development.
2008,
Pubmed Nasevicius,
Effective targeted gene 'knockdown' in zebrafish.
2000,
Pubmed Ng,
Oculofaciocardiodental and Lenz microphthalmia syndromes result from distinct classes of mutations in BCOR.
2004,
Pubmed Ohsaki,
Expression of the Vax family homeobox genes suggests multiple roles in eye development.
1999,
Pubmed
,
Xenbase Otaki,
The proto-oncogene BCL6 promotes survival of olfactory sensory neurons.
2010,
Pubmed Otaki,
The proto-oncogene BCL-6 is expressed in olfactory sensory neurons.
2005,
Pubmed Phan,
The BCL6 proto-oncogene suppresses p53 expression in germinal-centre B cells.
2004,
Pubmed Porges,
Autosomal dominant typical coloboma associated with unilateral pseudoptosis, myopia and cataract.
1995,
Pubmed Rao,
Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide.
2005,
Pubmed Robu,
p53 activation by knockdown technologies.
2007,
Pubmed Sakano,
BCL6 canalizes Notch-dependent transcription, excluding Mastermind-like1 from selected target genes during left-right patterning.
2010,
Pubmed
,
Xenbase Schulze,
Rare dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients.
1999,
Pubmed Seyfert,
Transcriptional repression by the proto-oncogene BCL-6.
1996,
Pubmed Shvarts,
A senescence rescue screen identifies BCL6 as an inhibitor of anti-proliferative p19(ARF)-p53 signaling.
2002,
Pubmed Stadler,
Histone deacetylase 1 is required for cell cycle exit and differentiation in the zebrafish retina.
2005,
Pubmed Sterner,
Acetylation of histones and transcription-related factors.
2000,
Pubmed Take-uchi,
Hedgehog signalling maintains the optic stalk-retinal interface through the regulation of Vax gene activity.
2003,
Pubmed
,
Xenbase Thisse,
High-resolution in situ hybridization to whole-mount zebrafish embryos.
2008,
Pubmed Thisse,
Spatial and temporal expression of the zebrafish genome by large-scale in situ hybridization screening.
2004,
Pubmed Torres,
Pax2 contributes to inner ear patterning and optic nerve trajectory.
1996,
Pubmed Tsukada,
Histone demethylation by a family of JmjC domain-containing proteins.
2006,
Pubmed van der Velden,
The Polycomb group protein Ring1b is essential for pectoral fin development.
2012,
Pubmed Viringipurampeer,
Pax2 regulates a fadd-dependent molecular switch that drives tissue fusion during eye development.
2012,
Pubmed Wallace,
Histone deacetylase activity in conjunction with E2F-1 and p53 regulates Apaf-1 expression in 661W cells and the retina.
2009,
Pubmed Wallace,
Histone deacetylase activity regulates apaf-1 and caspase 3 expression in the developing mouse retina.
2006,
Pubmed Wardle,
Zebrafish promoter microarrays identify actively transcribed embryonic genes.
2006,
Pubmed Wong,
Components of the SMRT corepressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARalpha, and BCL-6.
1998,
Pubmed Yamaguchi,
Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways.
2005,
Pubmed Ye,
Cloning of bcl-6, the locus involved in chromosome translocations affecting band 3q27 in B-cell lymphoma.
1993,
Pubmed
