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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: [+]
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, 2007, Pubmed [+]


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