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.
J Biol Chem
2010 Oct 01;28540:30814-24. doi: 10.1074/jbc.M110.142869.
Show Gene links
Show Anatomy links
ZFP423 coordinates Notch and bone morphogenetic protein signaling, selectively up-regulating Hes5 gene expression.
Masserdotti G
,
Badaloni A
,
Green YS
,
Croci L
,
Barili V
,
Bergamini G
,
Vetter ML
,
Consalez GG
.
???displayArticle.abstract???
Zinc finger protein 423 encodes a 30 Zn-finger transcription factor involved in cerebellar and olfactory development. ZFP423 is a known interactor of SMAD1-SMAD4 and of Collier/Olf-1/EBF proteins, and acts as a modifier of retinoic acid-induced differentiation. In the present article, we show that ZFP423 interacts with the Notch1 intracellular domain in mammalian cell lines and in Xenopus neurula embryos, to activate the expression of the Notch1 target Hes5/ESR1. This effect is antagonized by EBF transcription factors, both in cultured cells and in Xenopus embryos, and amplified in vitro by BMP4, suggesting that ZFP423 acts to integrate BMP and Notch signaling, selectively promoting their convergence onto the Hes5 gene promoter.
FIGURE 3. Selective, cooperative activation of ESR1 gene expression by Nact and ZFP423 in Xenopus embryos. A and B, whole mount in situ hybridization analysis of Xenopus Zfp423 gene expression in stage 17 (frontal view) and stage 22 (lateral view, head to the left) embryos, respectively: the gene is widely expressed starting in the neural plate/tube first (arrow), and then moving to the cranial neural crest (arrowhead). C, whole mount in situ hybridization analysis of ESR1 gene expression in embryos injected unilaterally (bracket) with Zfp423 (600 pg) and/or Nact (100 pg), as indicated. LacZ (blue stain) serves as an indicator of the injected side. Note strong ESR1 expression after coinjection of Nact and Zfp423. F, embryo injected unilaterally (bracket) with 1 ng of Zfp423. G, embryo injected unilaterally (bracket) with 1 ng of Zfp423 and 400 pg of DeltaStu, encoding a dominant negative Notch ligand. Note disappearance of ESR1 signal on the co-injected side. H and I, unilateral injection (bracket) of a Zfp423 morpholino oligonucleotide (H) and of a control morpholino (I) (see xperimental Procedures. Note disappearance of ESR1 signal on the injected side in embryos injected with Zfp423-specific morpholino unlike those injected with the control morpholino. J, Zfp423 overexpression selectively up-regulates ESR1 but not Hairy1 or Nrarp in Xenopus embryos. Whole mount in situ hybridization analysis of ESR1, Hairy1, and Nrarp gene expression in embryos injected unilaterally with Zfp423 (300 pg, arrow) in a dorsal blastomere. Note expanded ESR1 expression domain (J), but reduced/unaffected expression of Hairy1 (K) and Nrarp (L) on the injected side. Gfp was coinjected with Zfp423 as a lineage tracer (not shown).
FIGURE 6. EBF TFs reduce ZFP423-NICD-mediated Hes5 gene expression in vitro and in vivo. A, RT-qPCR analysis of Hes5 gene expression in P19 cells transfected with the indicated constructs. Note that Ebf1, Ebf2, or Ebf3 alone does not affect basal Hes5 expression. B, whole mount in situ hybridization analysis of ESR1 gene expression in embryos injected unilaterally (bracket) with Nact (100 pg) and Zfp423 (600 pg) and/or XEbf2 (100 pg) or XEbf3 (100 pg). E and F, whole mount in situ hybridization analysis of ESR1 gene expression in embryos injected unilaterally with XEbf2 (100 pg) or XEbf3 (100 pg), as indicated. Note slightly increased ESR1-positive cells in XEbf2- and XEbf3-injected embryos (arrow). B, LacZ (blue stain) serves as an indicator of the injected side.
Supplemental Figure 2. Zfp423 expression during Xenopus laevis development. Whole mount in situ hybridization analysis of Zfp423
gene expression in embryos at different stages of development (stage 17 and 22, dorsal view; stage 28 and 34 lateral view).
znf423 (zinc finger protein 423 ) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 17, dorsal view, anterior up.
znf423 (zinc finger protein 423 ) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 22, dorsal view, anterior up.
znf423 (zinc finger protein 423 ) gene expression in Xenopus laevis embryo, assayed via in situ hybridization, NF stage 28, lateral view, anteriorleft, dorsal up.
Alcaraz,
Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation.
2006, Pubmed
Alcaraz,
Zfp423 controls proliferation and differentiation of neural precursors in cerebellar vermis formation.
2006,
Pubmed
Anthony,
Brain lipid-binding protein is a direct target of Notch signaling in radial glial cells.
2005,
Pubmed
Artavanis-Tsakonas,
Notch signaling: cell fate control and signal integration in development.
1999,
Pubmed
Bray,
Notch signalling: a simple pathway becomes complex.
2006,
Pubmed
Brou,
A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE.
2000,
Pubmed
Buas,
Inhibition of myogenesis by Notch: evidence for multiple pathways.
2009,
Pubmed
Chalfie,
Green fluorescent protein as a marker for gene expression.
1994,
Pubmed
Cheng,
Zfp423/OAZ participates in a developmental switch during olfactory neurogenesis.
2007,
Pubmed
Cheng,
The transcription factor Zfp423/OAZ is required for cerebellar development and CNS midline patterning.
2007,
Pubmed
Chitnis,
Primary neurogenesis in Xenopus embryos regulated by a homologue of the Drosophila neurogenic gene Delta.
1995,
Pubmed
,
Xenbase
Chitnis,
Sensitivity of proneural genes to lateral inhibition affects the pattern of primary neurons in Xenopus embryos.
1996,
Pubmed
,
Xenbase
Chizhikov,
The roof plate regulates cerebellar cell-type specification and proliferation.
2006,
Pubmed
Chung,
Purkinje cell subtype specification in the cerebellar cortex: early B-cell factor 2 acts to repress the zebrin II-positive Purkinje cell phenotype.
2008,
Pubmed
Coffman,
Expression of an extracellular deletion of Xotch diverts cell fate in Xenopus embryos.
1993,
Pubmed
,
Xenbase
Corradi,
Hypogonadotropic hypogonadism and peripheral neuropathy in Ebf2-null mice.
2003,
Pubmed
Croci,
Local insulin-like growth factor I expression is essential for Purkinje neuron survival at birth.
2011,
Pubmed
Croci,
A key role for the HLH transcription factor EBF2COE2,O/E-3 in Purkinje neuron migration and cerebellar cortical topography.
2006,
Pubmed
,
Xenbase
Dahlqvist,
Functional Notch signaling is required for BMP4-induced inhibition of myogenic differentiation.
2003,
Pubmed
Davis,
Vertebrate hairy and Enhancer of split related proteins: transcriptional repressors regulating cellular differentiation and embryonic patterning.
2001,
Pubmed
,
Xenbase
Davis,
Role of Olf-1 and Pax-6 transcription factors in neurodevelopment.
1996,
Pubmed
Dawson,
Specificity for the hairy/enhancer of split basic helix-loop-helix (bHLH) proteins maps outside the bHLH domain and suggests two separable modes of transcriptional repression.
1995,
Pubmed
,
Xenbase
Dubois,
XCoe2, a transcription factor of the Col/Olf-1/EBF family involved in the specification of primary neurons in Xenopus.
1998,
Pubmed
,
Xenbase
Fryer,
Mastermind mediates chromatin-specific transcription and turnover of the Notch enhancer complex.
2002,
Pubmed
,
Xenbase
Garcia-Dominguez,
Ebf gene function is required for coupling neuronal differentiation and cell cycle exit.
2003,
Pubmed
,
Xenbase
Grishina,
BMP7 inhibits branching morphogenesis in the prostate gland and interferes with Notch signaling.
2005,
Pubmed
Hata,
OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways.
2000,
Pubmed
,
Xenbase
Hatakeyama,
Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation.
2004,
Pubmed
Henke,
Neurog2 is a direct downstream target of the Ptf1a-Rbpj transcription complex in dorsal spinal cord.
2009,
Pubmed
Hsieh,
CIR, a corepressor linking the DNA binding factor CBF1 to the histone deacetylase complex.
1999,
Pubmed
Huang,
ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome.
2009,
Pubmed
Itoh,
Synergy and antagonism between Notch and BMP receptor signaling pathways in endothelial cells.
2004,
Pubmed
Jarriault,
Signalling downstream of activated mammalian Notch.
1995,
Pubmed
Jennings,
The Notch signalling pathway is required for Enhancer of split bHLH protein expression during neurogenesis in the Drosophila embryo.
1994,
Pubmed
Jensen,
Control of endodermal endocrine development by Hes-1.
2000,
Pubmed
Kadesch,
Notch signaling: the demise of elegant simplicity.
2004,
Pubmed
Kageyama,
The Hes gene family: repressors and oscillators that orchestrate embryogenesis.
2007,
Pubmed
Kageyama,
Dynamic Notch signaling in neural progenitor cells and a revised view of lateral inhibition.
2008,
Pubmed
Krebs,
The Nrarp gene encodes an ankyrin-repeat protein that is transcriptionally regulated by the notch signaling pathway.
2001,
Pubmed
,
Xenbase
Ku,
OAZ regulates bone morphogenetic protein signaling through Smad6 activation.
2006,
Pubmed
Lamar,
The Notch targets Esr1 and Esr10 are differentially regulated in Xenopus neural precursors.
2005,
Pubmed
,
Xenbase
Lamar,
Nrarp is a novel intracellular component of the Notch signaling pathway.
2001,
Pubmed
,
Xenbase
Liu,
Bone morphogenetic protein signalling and vertebrate nervous system development.
2005,
Pubmed
Lowell,
Notch promotes neural lineage entry by pluripotent embryonic stem cells.
2006,
Pubmed
Machold,
Antagonism between Notch and bone morphogenetic protein receptor signaling regulates neurogenesis in the cerebellar rhombic lip.
2007,
Pubmed
Millen,
Cerebellar development and disease.
2008,
Pubmed
Mumm,
A ligand-induced extracellular cleavage regulates gamma-secretase-like proteolytic activation of Notch1.
2000,
Pubmed
Ohtsuka,
Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation.
1999,
Pubmed
Ohtsuka,
Visualization of embryonic neural stem cells using Hes promoters in transgenic mice.
2006,
Pubmed
Ohtsuka,
Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain.
2001,
Pubmed
Pozzoli,
Xebf3 is a regulator of neuronal differentiation during primary neurogenesis in Xenopus.
2001,
Pubmed
,
Xenbase
Sasai,
Two mammalian helix-loop-helix factors structurally related to Drosophila hairy and Enhancer of split.
1992,
Pubmed
Schroeter,
Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain.
1998,
Pubmed
Skarnes,
A public gene trap resource for mouse functional genomics.
2004,
Pubmed
Takizawa,
Enhanced gene activation by Notch and BMP signaling cross-talk.
2003,
Pubmed
Tsai,
Identification of DNA recognition sequences and protein interaction domains of the multiple-Zn-finger protein Roaz.
1998,
Pubmed
Tsai,
Cloning and functional characterization of Roaz, a zinc finger protein that interacts with O/E-1 to regulate gene expression: implications for olfactory neuronal development.
1997,
Pubmed
Turner,
Expression of achaete-scute homolog 3 in Xenopus embryos converts ectodermal cells to a neural fate.
1994,
Pubmed
,
Xenbase
Vincent,
Analysis of neuronal gene expression with laser capture microdissection.
2002,
Pubmed
Wallberg,
p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro.
2002,
Pubmed
Wang,
Molecular cloning of the olfactory neuronal transcription factor Olf-1 by genetic selection in yeast.
1993,
Pubmed
Wang,
The characterization of the Olf-1/EBF-like HLH transcription factor family: implications in olfactory gene regulation and neuronal development.
1997,
Pubmed
Warming,
Zfp423 is required for normal cerebellar development.
2006,
Pubmed
Wettstein,
The Xenopus homolog of Drosophila Suppressor of Hairless mediates Notch signaling during primary neurogenesis.
1997,
Pubmed
,
Xenbase
Wu,
MAML1, a human homologue of Drosophila mastermind, is a transcriptional co-activator for NOTCH receptors.
2000,
Pubmed
