XB-ART-45396
Mech Dev
September 1, 2012;
129
(9-12):
324-38.
Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis.
Barnett C
,
Yazgan O
,
Kuo HC
,
Malakar S
,
Thomas T
,
Fitzgerald A
,
Harbour W
,
Henry JJ
,
Krebs JE
.
Abstract
Williams Syndrome Transcription Factor (WSTF) is one of ∼25 haplodeficient genes in patients with the complex developmental disorder Williams Syndrome (WS). WS results in visual/spatial processing defects, cognitive impairment, unique behavioral phenotypes, characteristic "elfin" facial features, low muscle tone and heart defects. WSTF exists in several chromatin remodeling complexes and has roles in transcription, replication, and repair. Chromatin remodeling is essential during embryogenesis, but WSTF''s role in vertebrate development is poorly characterized. To investigate the developmental role of WSTF, we knocked down WSTF in Xenopus laevis embryos using a morpholino that targets WSTF mRNA. BMP4 shows markedly increased and spatially aberrant expression in WSTF-deficient embryos, while SHH, MRF4, PAX2, EPHA4 and SOX2 expression are severely reduced, coupled with defects in a number of developing embryonic structures and organs. WSTF-deficient embryos display defects in anterior neural development. Induction of the neural crest, measured by expression of the neural crest-specific genes SNAIL and SLUG, is unaffected by WSTF depletion. However, at subsequent stages WSTF knockdown results in a severe defect in neural crest migration and/or maintenance. Consistent with a maintenance defect, WSTF knockdowns display a specific pattern of increased apoptosis at the tailbud stage in regions corresponding to the path of cranial neural crest migration. Our work is the first to describe a role for WSTF in proper neural crest function, and suggests that neural crest defects resulting from WSTF haploinsufficiency may be a major contributor to the pathoembryology of WS.
PubMed ID: 22691402
PMC ID: PMC3459152
Article link: Mech Dev
Grant support: [+]
R01 EY009844 NEI NIH HHS , EY016029 NEI NIH HHS , EY09844 NEI NIH HHS , P20RR016466 NCRR NIH HHS , R15 EY016027 NEI NIH HHS , P20 GM103395 NIGMS NIH HHS , P20 RR016466 NCRR NIH HHS
Species referenced: Xenopus
Genes referenced: baz1b bmp4 epha4 myf6 myh3 ncam1 pax2 shh snai1 snai2 sox2
GO keywords: cytoplasmic chromatin
Morpholinos: baz1b MO1
Disease Ontology terms: Williams-Beuren syndrome
OMIMs: WILLIAMS-BEUREN SYNDROME; WBS
Article Images: [+] show captions
References [+] :
Agathocleous,
A general role of hedgehog in the regulation of proliferation.
2007, Pubmed
Agathocleous,
A general role of hedgehog in the regulation of proliferation.
2007,
Pubmed
Agathocleous, A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina. 2009, Pubmed , Xenbase
Ahlgren, Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. 2002, Pubmed , Xenbase
Ahlgren, Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. 2000, Pubmed
Ali, Abnormal extraocular muscle anatomy in a case of Williams-Beuren Syndrome. 2009, Pubmed
Archer, Interaction of Sox1, Sox2, Sox3 and Oct4 during primary neurogenesis. 2011, Pubmed , Xenbase
Ashe, A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development. 2009, Pubmed
Aybar, Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. 2002, Pubmed , Xenbase
Bajpai, CHD7 cooperates with PBAF to control multipotent neural crest formation. 2010, Pubmed , Xenbase
Bakrania, Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. 2008, Pubmed
Barnett, WSTF does it all: a multifunctional protein in transcription, repair, and replication. 2011, Pubmed
Basch, Neural crest inducing signals. 2006, Pubmed
Biesecker, Renal insufficiency in Williams syndrome. 1987, Pubmed
Briscoe, Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. 1999, Pubmed
Campuzano, Patterning of the Drosophila nervous system: the achaete-scute gene complex. 1992, Pubmed
Carroll, Synergism between Pax-8 and lim-1 in embryonic kidney development. 1999, Pubmed , Xenbase
Cavallaro, Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants. 2008, Pubmed
Chiang, Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. 1996, Pubmed
Creuzet, Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton. 2002, Pubmed
Cus, Cloning and developmental expression of WSTF during Xenopus laevis embryogenesis. 2006, Pubmed , Xenbase
Dale, Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. 1992, Pubmed , Xenbase
Delgado-Olguín, Chromatin structure of pluripotent stem cells and induced pluripotent stem cells. 2011, Pubmed
Dickinson, Positioning the extreme anterior in Xenopus: cement gland, primary mouth and anterior pituitary. 2007, Pubmed , Xenbase
Dirscherl, Neural and eye-specific defects associated with loss of the imitation switch (ISWI) chromatin remodeler in Xenopus laevis. 2005, Pubmed , Xenbase
Dressler, Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. 1990, Pubmed
Dubourg, Holoprosencephaly. 2007, Pubmed
Enkhmandakh, Essential functions of the Williams-Beuren syndrome-associated TFII-I genes in embryonic development. 2009, Pubmed
Fazzio, Control of embryonic stem cell identity by nucleosome remodeling enzymes. 2010, Pubmed
Gans, Neural crest and the origin of vertebrates: a new head. 2010, Pubmed
Grocott, Neural crest cells organize the eye via TGF-β and canonical Wnt signalling. 2011, Pubmed
Harland, In situ hybridization: an improved whole-mount method for Xenopus embryos. 1992, Pubmed , Xenbase
Heller, Xenopus Pax-2 displays multiple splice forms during embryogenesis and pronephric kidney development. 1998, Pubmed , Xenbase
Hemmati-Brivanlou, Ventral mesodermal patterning in Xenopus embryos: expression patterns and activities of BMP-2 and BMP-4. 1995, Pubmed , Xenbase
Heng, Transcription factors for the modulation of pluripotency and reprogramming. 2011, Pubmed
Hensey, Programmed cell death during Xenopus development: a spatio-temporal analysis. 1998, Pubmed , Xenbase
Hogan, Bone morphogenetic proteins in development. 1996, Pubmed , Xenbase
Howald, Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions. 2006, Pubmed
Hu, Restriction of BMP4 activity domains in the developing neural tube of the mouse embryo. 2004, Pubmed
Hutson, Model systems for the study of heart development and disease. Cardiac neural crest and conotruncal malformations. 2007, Pubmed
Iwao, Fate mapping of neural crest cells during eye development using a protein 0 promoter-driven transgenic technique. 2008, Pubmed
Jones, Bone morphogenetic protein-4 (BMP-4) acts during gastrula stages to cause ventralization of Xenopus embryos. 1996, Pubmed , Xenbase
Kondoh, SOX-partner code for cell specification: Regulatory target selection and underlying molecular mechanisms. 2010, Pubmed
Li Song, Two Pax2/5/8-binding sites in Engrailed2 are required for proper initiation of endogenous mid-hindbrain expression. 2000, Pubmed
Lu, A novel human gene, WSTF, is deleted in Williams syndrome. 1999, Pubmed
Manley, Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands. 1998, Pubmed , Xenbase
Martínez-Barberá, Cloning and expression of three members of the zebrafish Bmp family: Bmp2a, Bmp2b and Bmp4. 1997, Pubmed , Xenbase
Mayor, Development of neural crest in Xenopus. 1999, Pubmed , Xenbase
Mayor, Induction of the prospective neural crest of Xenopus. 1995, Pubmed , Xenbase
Mayor, Distinct elements of the xsna promoter are required for mesodermal and ectodermal expression. 1994, Pubmed , Xenbase
Merla, Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes. 2006, Pubmed
Murdoch, The relationship between sonic Hedgehog signaling, cilia, and neural tube defects. 2010, Pubmed
Müller, Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo. 2007, Pubmed
Nieto, Control of cell behavior during vertebrate development by Slug, a zinc finger gene. 1994, Pubmed
Noden, Neural crest cells and the community of plan for craniofacial development: historical debates and current perspectives. 2006, Pubmed
Osborne, Animal models of Williams syndrome. 2010, Pubmed
Owens, Genome-wide linkage identifies novel modifier loci of aganglionosis in the Sox10Dom model of Hirschsprung disease. 2005, Pubmed
Pagon, Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. 1981, Pubmed
Park, Ectopic EphA4 receptor induces posterior protrusions via FGF signaling in Xenopus embryos. 2004, Pubmed , Xenbase
Patten, The role of Sonic hedgehog in neural tube patterning. 2000, Pubmed
Pevny, Sox2 roles in neural stem cells. 2010, Pubmed
Pober, Renal findings in 40 individuals with Williams syndrome. 1993, Pubmed
Prykhozhij, In the absence of Sonic hedgehog, p53 induces apoptosis and inhibits retinal cell proliferation, cell-cycle exit and differentiation in zebrafish. 2010, Pubmed
Roelink, Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. 1995, Pubmed
Ruhin, Patterning of the hyoid cartilage depends upon signals arising from the ventral foregut endoderm. 2003, Pubmed
Safa, Better late than never: diagnosis and successful treatment in late adulthood of supravalvular aortic stenosis secondary to Williams-Beuren syndrome. 2011, Pubmed
Sauka-Spengler, A gene regulatory network orchestrates neural crest formation. 2008, Pubmed
Sefton, Conserved and divergent roles for members of the Snail family of transcription factors in the chick and mouse embryo. 1998, Pubmed
Selicorni, Thyroid anomalies in Williams syndrome: investigation of 95 patients. 2006, Pubmed
Serra, Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation. 2007, Pubmed
Sive, Synthesis and purification of digoxigenin-labeled RNA probes for in situ hybridization. 2011, Pubmed
Smith, The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. 1997, Pubmed , Xenbase
Steventon, Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction. 2009, Pubmed , Xenbase
Sugayama, Renal and urinary findings in 20 patients with Williams-Beuren syndrome diagnosed by fluorescence in situ hybridization (FISH). 2004, Pubmed
Varga, The phylogenesis and ontogenesis of the human pharyngeal region focused on the thymus, parathyroid, and thyroid glands. 2009, Pubmed
Wawersik, Conditional BMP inhibition in Xenopus reveals stage-specific roles for BMPs in neural and neural crest induction. 2004, Pubmed , Xenbase
Wilson, Induction of epidermis and inhibition of neural fate by Bmp-4. 1995, Pubmed , Xenbase
Winning, Pagliaccio, a member of the Eph family of receptor tyrosine kinase genes, has localized expression in a subset of neural crest and neural tissues in Xenopus laevis embryos. 1994, Pubmed , Xenbase
Winter, The spectrum of ocular features in the Williams-Beuren syndrome. 1996, Pubmed
Xu, Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain. 1996, Pubmed , Xenbase
Yamada, Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate. 1993, Pubmed
Yoshimura, Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF). 2009, Pubmed
Agathocleous, A directional Wnt/beta-catenin-Sox2-proneural pathway regulates the transition from proliferation to differentiation in the Xenopus retina. 2009, Pubmed , Xenbase
Ahlgren, Sonic hedgehog rescues cranial neural crest from cell death induced by ethanol exposure. 2002, Pubmed , Xenbase
Ahlgren, Inhibition of sonic hedgehog signaling in vivo results in craniofacial neural crest cell death. 2000, Pubmed
Ali, Abnormal extraocular muscle anatomy in a case of Williams-Beuren Syndrome. 2009, Pubmed
Archer, Interaction of Sox1, Sox2, Sox3 and Oct4 during primary neurogenesis. 2011, Pubmed , Xenbase
Ashe, A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development. 2009, Pubmed
Aybar, Snail precedes slug in the genetic cascade required for the specification and migration of the Xenopus neural crest. 2002, Pubmed , Xenbase
Bajpai, CHD7 cooperates with PBAF to control multipotent neural crest formation. 2010, Pubmed , Xenbase
Bakrania, Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. 2008, Pubmed
Barnett, WSTF does it all: a multifunctional protein in transcription, repair, and replication. 2011, Pubmed
Basch, Neural crest inducing signals. 2006, Pubmed
Biesecker, Renal insufficiency in Williams syndrome. 1987, Pubmed
Briscoe, Homeobox gene Nkx2.2 and specification of neuronal identity by graded Sonic hedgehog signalling. 1999, Pubmed
Campuzano, Patterning of the Drosophila nervous system: the achaete-scute gene complex. 1992, Pubmed
Carroll, Synergism between Pax-8 and lim-1 in embryonic kidney development. 1999, Pubmed , Xenbase
Cavallaro, Impaired generation of mature neurons by neural stem cells from hypomorphic Sox2 mutants. 2008, Pubmed
Chiang, Cyclopia and defective axial patterning in mice lacking Sonic hedgehog gene function. 1996, Pubmed
Creuzet, Negative effect of Hox gene expression on the development of the neural crest-derived facial skeleton. 2002, Pubmed
Cus, Cloning and developmental expression of WSTF during Xenopus laevis embryogenesis. 2006, Pubmed , Xenbase
Dale, Bone morphogenetic protein 4: a ventralizing factor in early Xenopus development. 1992, Pubmed , Xenbase
Delgado-Olguín, Chromatin structure of pluripotent stem cells and induced pluripotent stem cells. 2011, Pubmed
Dickinson, Positioning the extreme anterior in Xenopus: cement gland, primary mouth and anterior pituitary. 2007, Pubmed , Xenbase
Dirscherl, Neural and eye-specific defects associated with loss of the imitation switch (ISWI) chromatin remodeler in Xenopus laevis. 2005, Pubmed , Xenbase
Dressler, Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system. 1990, Pubmed
Dubourg, Holoprosencephaly. 2007, Pubmed
Enkhmandakh, Essential functions of the Williams-Beuren syndrome-associated TFII-I genes in embryonic development. 2009, Pubmed
Fazzio, Control of embryonic stem cell identity by nucleosome remodeling enzymes. 2010, Pubmed
Gans, Neural crest and the origin of vertebrates: a new head. 2010, Pubmed
Grocott, Neural crest cells organize the eye via TGF-β and canonical Wnt signalling. 2011, Pubmed
Harland, In situ hybridization: an improved whole-mount method for Xenopus embryos. 1992, Pubmed , Xenbase
Heller, Xenopus Pax-2 displays multiple splice forms during embryogenesis and pronephric kidney development. 1998, Pubmed , Xenbase
Hemmati-Brivanlou, Ventral mesodermal patterning in Xenopus embryos: expression patterns and activities of BMP-2 and BMP-4. 1995, Pubmed , Xenbase
Heng, Transcription factors for the modulation of pluripotency and reprogramming. 2011, Pubmed
Hensey, Programmed cell death during Xenopus development: a spatio-temporal analysis. 1998, Pubmed , Xenbase
Hogan, Bone morphogenetic proteins in development. 1996, Pubmed , Xenbase
Howald, Two high throughput technologies to detect segmental aneuploidies identify new Williams-Beuren syndrome patients with atypical deletions. 2006, Pubmed
Hu, Restriction of BMP4 activity domains in the developing neural tube of the mouse embryo. 2004, Pubmed
Hutson, Model systems for the study of heart development and disease. Cardiac neural crest and conotruncal malformations. 2007, Pubmed
Iwao, Fate mapping of neural crest cells during eye development using a protein 0 promoter-driven transgenic technique. 2008, Pubmed
Jones, Bone morphogenetic protein-4 (BMP-4) acts during gastrula stages to cause ventralization of Xenopus embryos. 1996, Pubmed , Xenbase
Kondoh, SOX-partner code for cell specification: Regulatory target selection and underlying molecular mechanisms. 2010, Pubmed
Li Song, Two Pax2/5/8-binding sites in Engrailed2 are required for proper initiation of endogenous mid-hindbrain expression. 2000, Pubmed
Lu, A novel human gene, WSTF, is deleted in Williams syndrome. 1999, Pubmed
Manley, Hox group 3 paralogs regulate the development and migration of the thymus, thyroid, and parathyroid glands. 1998, Pubmed , Xenbase
Martínez-Barberá, Cloning and expression of three members of the zebrafish Bmp family: Bmp2a, Bmp2b and Bmp4. 1997, Pubmed , Xenbase
Mayor, Development of neural crest in Xenopus. 1999, Pubmed , Xenbase
Mayor, Induction of the prospective neural crest of Xenopus. 1995, Pubmed , Xenbase
Mayor, Distinct elements of the xsna promoter are required for mesodermal and ectodermal expression. 1994, Pubmed , Xenbase
Merla, Submicroscopic deletion in patients with Williams-Beuren syndrome influences expression levels of the nonhemizygous flanking genes. 2006, Pubmed
Murdoch, The relationship between sonic Hedgehog signaling, cilia, and neural tube defects. 2010, Pubmed
Müller, Bone morphogenetic proteins specify the retinal pigment epithelium in the chick embryo. 2007, Pubmed
Nieto, Control of cell behavior during vertebrate development by Slug, a zinc finger gene. 1994, Pubmed
Noden, Neural crest cells and the community of plan for craniofacial development: historical debates and current perspectives. 2006, Pubmed
Osborne, Animal models of Williams syndrome. 2010, Pubmed
Owens, Genome-wide linkage identifies novel modifier loci of aganglionosis in the Sox10Dom model of Hirschsprung disease. 2005, Pubmed
Pagon, Coloboma, congenital heart disease, and choanal atresia with multiple anomalies: CHARGE association. 1981, Pubmed
Park, Ectopic EphA4 receptor induces posterior protrusions via FGF signaling in Xenopus embryos. 2004, Pubmed , Xenbase
Patten, The role of Sonic hedgehog in neural tube patterning. 2000, Pubmed
Pevny, Sox2 roles in neural stem cells. 2010, Pubmed
Pober, Renal findings in 40 individuals with Williams syndrome. 1993, Pubmed
Prykhozhij, In the absence of Sonic hedgehog, p53 induces apoptosis and inhibits retinal cell proliferation, cell-cycle exit and differentiation in zebrafish. 2010, Pubmed
Roelink, Floor plate and motor neuron induction by different concentrations of the amino-terminal cleavage product of sonic hedgehog autoproteolysis. 1995, Pubmed
Ruhin, Patterning of the hyoid cartilage depends upon signals arising from the ventral foregut endoderm. 2003, Pubmed
Safa, Better late than never: diagnosis and successful treatment in late adulthood of supravalvular aortic stenosis secondary to Williams-Beuren syndrome. 2011, Pubmed
Sauka-Spengler, A gene regulatory network orchestrates neural crest formation. 2008, Pubmed
Sefton, Conserved and divergent roles for members of the Snail family of transcription factors in the chick and mouse embryo. 1998, Pubmed
Selicorni, Thyroid anomalies in Williams syndrome: investigation of 95 patients. 2006, Pubmed
Serra, Functional interdependence at the chromatin level between the MKK6/p38 and IGF1/PI3K/AKT pathways during muscle differentiation. 2007, Pubmed
Sive, Synthesis and purification of digoxigenin-labeled RNA probes for in situ hybridization. 2011, Pubmed
Smith, The EphA4 and EphB1 receptor tyrosine kinases and ephrin-B2 ligand regulate targeted migration of branchial neural crest cells. 1997, Pubmed , Xenbase
Steventon, Differential requirements of BMP and Wnt signalling during gastrulation and neurulation define two steps in neural crest induction. 2009, Pubmed , Xenbase
Sugayama, Renal and urinary findings in 20 patients with Williams-Beuren syndrome diagnosed by fluorescence in situ hybridization (FISH). 2004, Pubmed
Varga, The phylogenesis and ontogenesis of the human pharyngeal region focused on the thymus, parathyroid, and thyroid glands. 2009, Pubmed
Wawersik, Conditional BMP inhibition in Xenopus reveals stage-specific roles for BMPs in neural and neural crest induction. 2004, Pubmed , Xenbase
Wilson, Induction of epidermis and inhibition of neural fate by Bmp-4. 1995, Pubmed , Xenbase
Winning, Pagliaccio, a member of the Eph family of receptor tyrosine kinase genes, has localized expression in a subset of neural crest and neural tissues in Xenopus laevis embryos. 1994, Pubmed , Xenbase
Winter, The spectrum of ocular features in the Williams-Beuren syndrome. 1996, Pubmed
Xu, Expression of truncated Sek-1 receptor tyrosine kinase disrupts the segmental restriction of gene expression in the Xenopus and zebrafish hindbrain. 1996, Pubmed , Xenbase
Yamada, Control of cell pattern in the neural tube: motor neuron induction by diffusible factors from notochord and floor plate. 1993, Pubmed
Yoshimura, Distinct function of 2 chromatin remodeling complexes that share a common subunit, Williams syndrome transcription factor (WSTF). 2009, Pubmed