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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 324-338 |
| Number of pages | 15 |
| Journal | Mechanisms of Development |
| Volume | 129 |
| Issue number | 9-12 |
| DOIs | |
| State | Published - Sep 1 2012 |
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Keywords
- BAZ1b
- Chromatin remodeler
- Neural crest
- WSTF
- Williams Syndrome
- Xenopus
ASJC Scopus subject areas
- Embryology
- Developmental Biology
Cite this
Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis. / Barnett, Chris; Yazgan, Oya; Kuo, Hui Ching; Malakar, Sreepurna; Thomas, Trevor; Fitzgerald, Amanda; Harbour, William; Henry, Jonathan J.; Krebs, Jocelyn E.
In: Mechanisms of Development, Vol. 129, No. 9-12, 01.09.2012, p. 324-338.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis
AU - Barnett, Chris
AU - Yazgan, Oya
AU - Kuo, Hui Ching
AU - Malakar, Sreepurna
AU - Thomas, Trevor
AU - Fitzgerald, Amanda
AU - Harbour, William
AU - Henry, Jonathan J.
AU - Krebs, Jocelyn E.
PY - 2012/9/1
Y1 - 2012/9/1
N2 - 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.
AB - 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.
KW - BAZ1b
KW - Chromatin remodeler
KW - Neural crest
KW - WSTF
KW - Williams Syndrome
KW - Xenopus
UR - http://www.scopus.com/inward/record.url?scp=84867894480&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867894480&partnerID=8YFLogxK
U2 - 10.1016/j.mod.2012.06.001
DO - 10.1016/j.mod.2012.06.001
M3 - Article
C2 - 22691402
AN - SCOPUS:84867894480
VL - 129
SP - 324
EP - 338
JO - Mechanisms of Development
JF - Mechanisms of Development
SN - 0925-4773
IS - 9-12
ER -