Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis.
Williams Syndrome Transcription Factor is critical for neural crest cell function in Xenopus laevis.
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DOI：
10.1016/j.mod.2012.06.001
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发表时间：
2012-09
影响因子：
2.6
通讯作者：
Krebs, Jocelyn E.
中科院分区：
文献类型：
--
作者：
Barnett, Chris;Yazgan, Oya;Kuo, Hui-Ching;Malakar, Sreepurna;Thomas, Trevor;Fitzgerald, Amanda;Harbour, William;Henry, Jonathan J.;Krebs, Jocelyn E.
威廉姆斯综合征转录因子（WSTF）是复杂发育障碍威廉姆斯综合征（WS）患者的~25个单倍缺陷基因之一。WS导致视觉/空间处理缺陷、认知障碍、独特的行为表型、特征性的“精灵”面部特征、低肌张力和心脏缺陷。WSTF存在于几种染色质重塑复合物中，并在转录、复制和修复中发挥作用。染色质重塑在胚胎发生过程中是必不可少的，但WSTF在脊椎动物发育中的作用还不清楚。为了研究WSTF的发育作用，我们敲低了WSTF在非洲爪蟾胚胎中使用的吗啉，目标WSTF mRNA。BMP 4在WSTF缺陷的胚胎中显示出显著增加和空间异常表达，而SHH、MRF 4、PAX 2、EPHA 4和SOX 2表达严重降低，伴随着许多发育中的胚胎结构和器官的缺陷。WSTF缺陷的胚胎显示前神经发育缺陷。通过神经嵴特异性基因SNAIL和SLUG的表达测量的神经嵴的诱导不受WSTF消耗的影响。然而，在随后的阶段，WSTF敲低导致神经嵴迁移和/或维持的严重缺陷。与维护缺陷一致，WSTF敲除在尾芽期对应于颅神经嵴迁移路径的区域显示特定的细胞凋亡增加模式。我们的工作是第一个描述WSTF在适当的神经嵴功能中的作用，并表明WSTF单倍不足导致的神经嵴缺陷可能是WS病理胚胎学的主要贡献者。
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.
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影响因子：
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作者：
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