Factors Regulating Inner Ear Specification
调节内耳规格的因素
基本信息
- 批准号:7032780
- 负责人:
- 金额:$ 26.95万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2005
- 资助国家:美国
- 起止时间:2005-12-14 至 2010-11-30
- 项目状态:已结题
- 来源:
- 关键词:DNA binding proteinWnt gene /proteinXenopusantisense nucleic acidbiological signal transductiondevelopmental geneticsembryogenesisgene expressiongenetic regulationhistologylabyrinthnonmammalian vertebrate embryologynucleoproteinsoligonucleotidesprotein protein interactionprotein quantitation /detectiontranscription factoryeast two hybrid system
项目摘要
DESCRIPTION (provided by applicant):
The vertebrate inner ear is a sensory organ implicated in hearing, balance and detection of acceleration. It develops from a thickening of the embryonic ectoderm known as the otic placode. Defining the molecular processes leading to specification of the otic placode is essential to understand inner ear development. Sox proteins comprise a large class of transcriptional regulators. One member of this family, Sox9, a well- established regulator of chondrogenesis and sex determination, is also one of the earliest genes expressed in the presumptive otic placode. Mutations in Sox9 result in campomelic dysplasia (CD), a fatal human disorder characterized by severe skeletal malformations and XY sex reversal. Reports of rare CD patients that survived indicate that they are also affected with sensorineural deafness, suggesting that Sox9 may play an important role in the development of the auditory system. We have shown that the otic expression of Sox9 in Xenopus is initiated early in the sensory layer of the ectoderm. In this tissue, Sox9 expression is regulated by Fgf and Wnt signaling and co-localizes with Pax8, one of the earliest gene expressed in response to otic placode inducing signals. Depletion of Sox9 protein in whole embryos using morpholino antisense oligonucleotides causes a dramatic loss of early and late otic markers, and in the most extreme cases these embryos fail to form a morphologically recognizable otic vesicle. The experiments below will test the following hypothesis: the transcription factor Sox9 is a key component of regulatory pathway required for inner ear specification. We propose: 1-To define the molecular regulators of Sox9 expression in the otic placode by establishing the origin of the signals activating Sox9 expression in the otic placode; and defining the requirement and sufficiency of Fgf and Wnt signaling for otic placode specification in whole embryos and animal explants. 2-To characterize the ear phenotype of Xenopus Sox9-deficient embryos 3-To identify Sox9-interacting partner molecules in the otic placode using a yeast two-hybrid screen, since Sox proteins are known to regulate their target genes through interaction with cell type-specific partner molecules.The characterization of such partner molecules should further our understanding of Sox9-mediated gene regulation in the context of the developing inner ear.
描述(由申请人提供):
脊椎动物的内耳是一种与听觉、平衡和加速度检测有关的感觉器官。它由称为耳基板的胚胎外胚层增厚发育而来。定义导致耳基板规范的分子过程对于了解内耳发育至关重要。 Sox 蛋白包含一大类转录调节因子。 Sox9 是该家族的成员之一,它是一种成熟的软骨形成和性别决定调节因子,也是在假定的耳基板中表达的最早的基因之一。 Sox9 突变会导致羊膜发育不良 (CD),这是一种致命的人类疾病,其特征是严重的骨骼畸形和 XY 性逆转。罕见的 CD 患者幸存的报告表明,他们也患有感音神经性耳聋,这表明 Sox9 可能在听觉系统的发育中发挥重要作用。我们已经证明,爪蟾中 Sox9 的耳表达是在外胚层感觉层的早期启动的。在该组织中,Sox9 表达受 Fgf 和 Wnt 信号传导调节,并与 Pax8 共定位,Pax8 是响应耳基板诱导信号而表达的最早基因之一。使用吗啉代反义寡核苷酸去除整个胚胎中的 Sox9 蛋白会导致早期和晚期耳标记物的显着损失,并且在最极端的情况下,这些胚胎无法形成形态可识别的耳小泡。下面的实验将检验以下假设:转录因子 Sox9 是内耳规范所需调节途径的关键组成部分。我们建议: 1-通过建立激活耳基板中 Sox9 表达的信号起源来定义耳基板中 Sox9 表达的分子调节因子;并定义整个胚胎和动物外植体中耳基板规范的 Fgf 和 Wnt 信号传导的要求和充分性。 2-表征非洲爪蟾 Sox9 缺陷胚胎的耳表型 3-使用酵母双杂交筛选鉴定耳基板中与 Sox9 相互作用的伴侣分子,因为已知 Sox 蛋白通过与细胞类型特异性伴侣分子相互作用来调节其靶基因。此类伴侣分子的表征应进一步加深我们对发育中内耳背景下 Sox9 介导的基因调控的理解。 耳朵。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jean-Pierre Saint-Jeannet其他文献
Jean-Pierre Saint-Jeannet的其他文献
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{{ truncateString('Jean-Pierre Saint-Jeannet', 18)}}的其他基金
Pathogenesis of craniofacial defects in Nager syndrome
Nager 综合征颅面缺损的发病机制
- 批准号:
9196936 - 财政年份:2016
- 资助金额:
$ 26.95万 - 项目类别:
Molecular control of cranial placode progenitor formation
颅板祖细胞形成的分子控制
- 批准号:
9181389 - 财政年份:2015
- 资助金额:
$ 26.95万 - 项目类别:
Factors Regulating Inner Ear Specification in Xenopus
调节非洲爪蟾内耳规格的因素
- 批准号:
7156965 - 财政年份:2005
- 资助金额:
$ 26.95万 - 项目类别:














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