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

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):

项目成果

期刊论文数量(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
调节内耳规格的因素
  • 批准号:
    7728250
  • 财政年份:
    2005
  • 资助金额:
    $ 26.95万
  • 项目类别:
Factors Regulating Inner Ear Specification
调节内耳规格的因素
  • 批准号:
    7534356
  • 财政年份:
    2005
  • 资助金额:
    $ 26.95万
  • 项目类别:
Factors Regulating Inner Ear Specification
调节内耳规格的因素
  • 批准号:
    7316089
  • 财政年份:
    2005
  • 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:
Control of Neural Crest Development in Xenopus
非洲爪蟾神经嵴发育的控制
  • 批准号:
    8097434
  • 财政年份:
    2002
  • 资助金额:
    $ 26.95万
  • 项目类别:
Control of neural crest development in Xenopus
非洲爪蟾神经嵴发育的控制
  • 批准号:
    6623896
  • 财政年份:
    2002
  • 资助金额:
    $ 26.95万
  • 项目类别:
Control of neural crest development in Xenopus
非洲爪蟾神经嵴发育的控制
  • 批准号:
    6845394
  • 财政年份:
    2002
  • 资助金额:
    $ 26.95万
  • 项目类别:
Control of neural crest development in Xenopus
非洲爪蟾神经嵴发育的控制
  • 批准号:
    7035889
  • 财政年份:
    2002
  • 资助金额:
    $ 26.95万
  • 项目类别:
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