Developmental origins of the inner ear sensory organs

内耳感觉器官的发育起源

• 批准号: 7449569
• 负责人: ANDRES COLLAZO
• 金额: $ 35.11万
• 依托单位: HOUSE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-29 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7449569
• 关键词: Ablation; Address; African; Amphibia; Anterior; Biological Assay; Brain; Cells; Complex; Congenital Abnormality; Defect; Development; Dorsal; Dyes; Ear; Electroporation; Embryo; Embryology; Embryonic Development; Equilibrium; Erinaceidae; Excision; Ganglia; Gene Expression; Gene Mutation; Genes; Goals; Hair Cells; Hearing; Image; Label; Labyrinth; Life; Location; Medicine; Modeling; Molecular; Mus; Myxoid cyst; Nobel Prize; Nose; Organ; Otic Placodes; Pattern; Play; Positioning Attribute; Rana; Reagent; Research Personnel; Role; Scientist; Sensory; Side; Signal Pathway; Signal Transduction; Signaling Molecule; Simple Epithelium; Staging; Structure; Study models; Tadpoles; Testing; Time; Tissues; Xenopus; Xenopus laevis; Xenopus sp.; Zebrafish; deafness; gene function; in vivo; inhibitor/antagonist; insight; loss of function; member; membranous labyrinth; nerve supply; otoconia; programs; smoothened signaling pathway; sound; tool

DESCRIPTION (provided by applicant): The inner ear is a highly asymmetrical sensory structure with clearly defined anterior-posterior (A-P) and dorsal-ventral (D-V) axes. How these axes arise during embryonic development from a simple epithelium, the otic placode, and the genes involved in this patterning are almost completely unknown. Inner ear sensory organs (consisting of mechanosensory hair cells) are precisely positioned within the nonsensory membranous labyrinth and represent a small percentage of actual ear tissue. Their position and orientation are vital for normal function in balance and hearing. Any problems during the development of this complex structure would result in balance or hearing deficits. Our long-term goal is to determine the molecular signaling pathways necessary for inner ear patterning. Advances in vital dyes, intravital imaging and gene function assays in the African clawed frog, Xenopus laevis, as well as the ease with which embryological manipulations can be done, combine to offer us the unique opportunity to address our proposed specific aims (SA) and hypotheses (HYP) in living embryos and tadpoles. SA 1: Determine which regions of the inner ear placode or otocyst are required for normal patterning. HYP. Dorsal and/or ventral signals are necessary for normal A-P patterning of the inner ear. SA 2: Role of Hedgehog (Hh) signaling in the patterning of the developing inner ear. HYP. Hh signaling, after otic placode formation, is required for both A-P and ventral patterning of the inner ear. SA 3: Role of canonical Wnt signaling in the patterning of the developing inner ear. HYP. Wnt signaling, after otocyst formation, plays a role in A-P as well as D-V patterning of the inner ear. Lay Summary: The lack of regenerative potential of the developing inner ear in contrast to other sensory organs, such as the nose, may help explain why deafness is one of the more common birth defects. A key question is not just which molecules induce the formation of hair cells (specialized cells in the ear that transduce sound to electrical inputs for the brain to interpret) but more important for actual hearing and balance is the need to form and place these new hair cells in precise positions in the newly formed inner ear. This proposal will identify which molecules are necessary for putting these hair cells in the right place so they can function in hearing and balance. The frog inner ear is very similar to ours so it provides a good model for studying inner ear development.

描述（由申请人提供）：内耳是一个高度不对称的感觉结构，具有明确定义的前后（A-P）轴和背腹（D-V）轴。这些轴在胚胎发育过程中如何从简单的上皮、耳基板以及参与这种模式的基因中产生的几乎完全未知。内耳感觉器官（由机械感觉毛细胞组成）精确定位在非感觉膜迷路内，仅占实际耳组织的一小部分。它们的位置和方向对于平衡和听力的正常功能至关重要。这种复杂结构发育过程中的任何问题都会导致平衡或听力缺陷。我们的长期目标是确定内耳模式所需的分子信号传导途径。非洲爪蛙（Xenopus laevis）活体染料、活体成像和基因功能测定方面的进步，以及胚胎操作的简便性，结合起来为我们提供了独特的机会来实现我们提出的具体目标（SA）和活胚胎和蝌蚪的假设（HYP）。 SA 1：确定正常模式需要内耳基板或耳囊的哪些区域。 HYP。背侧和/或腹侧信号对于内耳的正常 A-P 模式是必需的。 SA 2：Hedgehog (Hh) 信号传导在内耳发育模式中的作用。 HYP。耳基板形成后，Hh 信号传导对于内耳的 A-P 和腹侧模式都是必需的。 SA 3：典型 Wnt 信号传导在内耳发育模式中的作用。 HYP。耳囊形成后，Wnt 信号传导在内耳的 A-P 和 D-V 模式中发挥作用。外行总结：与其他感觉器官（例如鼻子）相比，发育中的内耳缺乏再生潜力，这可能有助于解释为什么耳聋是更常见的出生缺陷之一。一个关键问题不仅是哪些分子诱导毛细胞（耳朵中的特殊细胞，将声音转换为电输入供大脑解释）的形成，而且对于实际听力和平衡更重要的是形成和放置这些新毛发的需要细胞位于新形成的内耳中的精确位置。该提案将确定哪些分子是将这些毛细胞放置在正确位置所必需的，以便它们能够发挥听力和平衡功能。青蛙的内耳与我们的内耳非常相似，因此它为研究内耳发育提供了一个很好的模型。