Genetic Analysis of Inner Ear Development in tropicalis

描述（由申请人提供）：为了提高我们对耳朵发育及其潜在的分子和遗传相互作用的理解，我们正在对两栖动物热带爪蟾（Xenopus tropical alis）进行遗传筛选，这是一种最近引入的遗传模型动物。这项初步研究揭示了几个涉及耳形态、耳石形成和平衡/游泳行为的基因座。重要的是，在活胚中可以观察到热带天牛耳部形态发生的主要事件，极大地帮助筛选遗传缺陷。先前在耳朵发育方面的研究表明，从人类到青蛙，潜在的分子机制都很好地保守，这使得遗传上可适应的卵生热带狐猴成为一个有吸引力的模型动物，用于研究听力和平衡异常的原因以及潜在的分子和遗传相互作用。以前的内耳突变筛选已经在斑马鱼和老鼠身上完成，我们希望在非洲爪蟾身上找到重叠和不同的突变。在这个建议中，我们将识别和绘制影响耳朵的突变，并将它们与先前已知的候选基因联系起来，或者将它们识别为参与耳朵发育的新位点。我们将描述突变表型，集中在新的位点。这将建立热带爪蟾作为了解耳朵发育和疾病的有效新系统。正如项目公告所述，人类内耳的形成是复杂的，无论是正常发育还是发育障碍，人们都知之甚少。对内耳发育的理解将受益于对热带非洲爪蟾等模式生物的研究，在这些生物中，突变表型可以用来理解正常发育的潜在机制。

DESCRIPTION (provided by applicant): To advance our understanding of ear development and the underlying molecular and genetic interactions, we are undertaking a forward genetic screen in the amphibian Xenopus tropicalis, a recently introduced genetic model animal. This pilot study reveals several loci involved in ear morphology, otolith formation, and balancing/swimming behavior. Importantly, the major events of X. tropicalis ear morphogenesis can be observed externally in the living embryos, greatly aiding screens for genetic defects. Previous work in ear development has demonstrated that underlying molecular mechanisms are well conserved from human to frog, making genetically amenable and oviparous X. tropicalis an attractive model animal in which to study the causes of hearing and balance anomalies as well as underlying molecular and genetic interactions. Previous screens for inner ear mutants have been done in zebrafish and mouse, and we expect to find both overlapping and different mutations in Xenopus. In this proposal we shall identify and map mutations affecting the ear, and link them to previously known candidate genes, or identify them as new loci involved in ear development. We shall characterize the mutant phenotypes, concentrating on the novel loci. This will establish Xenopus tropicalis as an effective new system to understand ear development and disorders. As described in the Program Announcement, the formation of the human inner ear is complex, and both the normal development and developmental disorders are poorly understood. The understanding of inner ear development will benefit from studies in model organisms such as Xenopus tropicalis, where mutant phenotypes can be used to understand the underlying mechanisms for normal development.