期刊
MECHANISMS OF DEVELOPMENT
卷 129, 期 9-12, 页码 324-338出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.mod.2012.06.001
关键词
WSTF; Neural crest; Xenopus; Williams Syndrome; BAZ1b; Chromatin remodeler
资金
- NIH [EY016029, EY09844, P20RR016466]
- Whitehall Foundation [2007-08-79]
- Direct For Biological Sciences
- Div Of Biological Infrastructure [1005210] Funding Source: National Science Foundation
Williams Syndrome Transcription Factor (WSTF) is one of similar to 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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