Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination

Hilton, Emma; Manson, Forbes D.C.; Urquhart, Jill; Johnston, Jennifer J.; Slavotinek, Anne; Hedera, Peter; Stattin, Eva‐Lena; Nordgren, Ann; Biesecker, Leslie G.; Black, Graeme C M

doi:10.1093/hmg/ddm125

Cited by 48 publications

(57 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Like in frog (Hilton et al, 2007;Sakano et al, 2010), BCoR mutations randomize LR asymmetry in human embryos (Ng et al, 2004;Hilton et al, 2007), but this does not occur in mouse (Ye et al, 1997;Yoshida et al, 1999). The loss of brain asymmetry observed in mouse mutants with ciliary dyskinesia (Kawakami et al, 2008) is not observed in human patients (Kennedy et al, 1999;Tanaka et al, 1999;McManus et al, 2004;Afzelius and Stenram, 2006).…”

Section: The Mouse As a Model For Mammalian Asymmetrymentioning

confidence: 94%

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Vandenberg

Levin

2010

Developmental Dynamics

View full text Add to dashboard Cite

Consistent laterality is a crucial aspect of embryonic development, physiology, and behavior. While strides have been made in understanding unilaterally expressed genes and the asymmetries of organogenesis, early mechanisms are still poorly understood. One popular model centers on the structure and function of motile cilia and subsequent chiral extracellular fluid flow during gastrulation. Alternative models focus on intracellular roles of the cytoskeleton in driving asymmetries of physiological signals or asymmetric chromatid segregation, at much earlier stages. All three models trace the origin of asymmetry back to the chirality of cytoskeletal organizing centers, but significant controversy exists about how this intracellular chirality is amplified onto cell fields. Analysis of specific predictions of each model and crucial recent data on new mutants suggest that ciliary function may not be a broadly conserved, initiating event in left-right patterning. Many questions about embryonic left-right asymmetry remain open, offering fascinating avenues for further research in cell, developmental, and evolutionary biology. Developmental Dynamics 239:3131-3146,

show abstract

Section: The Mouse As a Model For Mammalian Asymmetrymentioning

confidence: 94%

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Vandenberg

Levin

2010

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…This is the first reported selective inhibitory mechanism of Notchmediated transcription. Although similar roles for the BCL6/BCoR complex have not been reported in mammals to date, it should be noted that mutations of human BCoR leads to the oculofaciocardiodental (OFCD) syndrome that includes defective laterality [142,154]. Although these interesting functions of Notch signaling have been observed, it still remains unclear whether the regulation of Notch signaling on the left side of Hensen's node observed in chick is conserved in other vertebrates, whether the role of Notch signaling in zebrafish ciliogenesis is conserved in other vertebrates, how Notch signaling is involved in ciliogenesis and how ESR1, a Notch target, inhibits expression of Pitx2 in the left LPM.…”

Section: Discussionmentioning

confidence: 90%

“…Knockdown of transcriptional repressor B cell lymphoma 6 (BCL6) or its co-repressor BCL6 co-repressor (BCoR) in Xenopus showed defects of LR asymmetry [91,142]. The expression of Pitx2 but not Xnr1, a homologue of Nodal, in the left LPM was suppressed in either BCL6 or BCoR knockdown embryos, because BCL6/BCoR complex blocks Notch signaling in the LPM by inhibiting transcription of selected Notch targets such as ESR1, a homologue of Hes5 [91].…”

Section: Roles Of Notch Signaling During Lr Asymmetric Determinationmentioning

confidence: 99%

The multiple roles of Notch signaling during left-right patterning

Kato

2011

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The establishment of left-right (LR) asymmetry is regulated by intricate signaling mechanisms during embryogenesis and this asymmetry is critical for morphogenesis as well as the positioning of internal organs within the organism. Recent progress including elucidation of ion transporters, leftward nodal flow, and regulation of asymmetric gene expression contributes to our understanding of how the breaking of the symmetry is initiated and how this laterality information is subsequently transmitted to the organ primordium. A number of developmental signaling pathways have been implicated in this complex process. In this review, we will focus on the roles of the Notch signaling pathway during development of LR asymmetry. The Notch signaling pathway is a short-range communication system between neighboring cells. While Notch signaling plays essential roles in regulating the morphogenesis of the node and left-specific expression of Nodal in the lateral plate mesoderm, a hallmark gene in LR patterning, Notch signaling also suppresses the expression of Pitx2 that is a direct downstream target of Nodal during later stages of development. This negative activity of Notch signaling towards left-specific activity was recently shown to be inhibited by the B cell lymphoma 6 (BCL6)/BCL6 co-repressor (BcoR) transcriptional repressor complex in a target-specific manner. The complex regulation of Notch-dependent gene expression for LR asymmetry will be highlighted in this review.

show abstract

“…OFCD comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities (Ng et al 2004). Moreover, dental disorders caused by OFCD have also been reported (Hilton et al 2007;Oberoi et al 2005). Interestingly, knockdown of the zebrafish (Danio rerio) ortholog of BCOR causes developmental perturbations of the eye, skeleton, and central nervous system; these characteristics are consistent with the human syndrome and suggest that BCOR is a key transcriptional regulator in early embryogenesis (Ng et al 2004).…”

Section: Introductionmentioning

confidence: 78%

“…Thus, this RNAi approach is likely to be a useful application in several model systems for further gene function studies. Mutations in BCOR cause OFCD, which is characterized by exceptionally long tooth roots (Hilton et al 2007;Ng et al 2004;Oberoi et al 2005;Wamstad and Bardwell 2007). In this study, we have performed tooth germ transplantation into the kidney to confirm the function of Bcor by knocking down the Bcor.…”

Section: Discussionmentioning

confidence: 99%

Function analysis of mesenchymal Bcor in tooth development by using RNA interference

et al. 2010

View full text Add to dashboard Cite

Teeth, an excellent model for studying organogenesis, develop from a series of epithelial-mesenchymal interactions that are mediated by a complex molecular network. Bcor (BCL-6 interacting corepressor) has recently been discovered, but little is known about its function in tooth development. Mutations in BCOR affect humans with oculofaciocardiodental syndrome, which is an X-linked dominant disorder with presumed male lethality and which comprises microphthalmia, congenital cataracts, radiculomegaly, and cardiac and digital abnormalities. In this study, the Bcor expression pattern has been intensively investigated during mouse molar development. Bcor is expressed in both dental epithelium and the mesenchyme at E11.5. To understand the function of Bcor, knockdown of Bcor has been examined by using lentivirus-mediated RNA interference. Silencing of Bcor expression in dental mesenchymal cells at E14.5 causes dentinogenesis defects and retardation of tooth root development. Thus, our results suggest that Bcor expressed in the mesenchyme plays crucial roles during early tooth development. The function of Bcor expressed in the epithelium remains to be elucidated.

show abstract

Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination

Cited by 48 publications

References 34 publications

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

Far from solved: A perspective on what we know about early mechanisms of left–right asymmetry

The multiple roles of Notch signaling during left-right patterning

Function analysis of mesenchymal Bcor in tooth development by using RNA interference

Contact Info

Product

Resources

About