Developmental origins of the inner ear sensory organs

内耳感觉器官的发育起源

• 批准号: 7242108
• 负责人: ANDRES COLLAZO
• 金额: $ 10万
• 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 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7242108
• 关键词: balance; hair; hearing; labyrinth

DESCRIPTION (provided by applicant): The inner ear is a highly asymmetrical sensory structure with clearly defined anterior-posterior, dorsal- ventral, and medial-lateral 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. The placode undergoes a great deal of growth, morphogenesis, differentiation and selective cell death to form the adult inner ear. 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: Characterize an embryonic manipulation resulting in mirror image duplicated inner ears. Hyp. Half ablations along the anterior-posterior axis and not removal of greater or lesser amounts are necessary to generate mirror image duplications. SA 2: Role of Hedgehog (Hh) signaling in the patterning of the developing inner ear. Hyp. Hh signaling is involved in anterior-posterior patterning. SA 3: Role of Wnt signaling in the patterning of the developing inner ear. Hyp. Canonical Wnt signaling is involved in dorsal-ventral patterning while the noncanonical, Planar Cell Polarity (PCP), pathway is involved in morphogenesis and hair cell orientations. The lack of regenerative potential of the developing inner ear in contrast to other placodes, such as the olfactory, may help explain why deafness is one of the more common birth defects as opposed to those in other sensory placode derived structures. A key question is not just which molecules induce the formation of hair cells 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.

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轴、背腹轴和内侧轴。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。基板经历大量的生长、形态发生、分化和选择性细胞死亡，形成成人内耳。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）和活体胚胎和蝌蚪中的假设（Hyp）。 SA 1：描述胚胎操作导致内耳镜像复制的特征。炒作。沿着前后轴进行半消融并且不去除或多或少的量对于产生镜像重复是必要的。 SA 2：Hedgehog (Hh) 信号传导在内耳发育模式中的作用。炒作。 Hh 信号传导参与前后模式。 SA 3：Wnt 信号传导在内耳发育模式中的作用。炒作。规范的 Wnt 信号传导参与背腹模式，而非规范的平面细胞极性 (PCP) 通路则参与形态发生和毛细胞方向。与其他基板（例如嗅觉）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，而不是其他感觉基板衍生结构的缺陷。一个关键问题不仅是哪些分子诱导毛细胞的形成，而且对于实际听力和平衡来说更重要的是需要形成这些新毛细胞并将其放置在新形成的内耳中的精确位置。