Molecular genetics of mammalian larynx and vocal fold development

摘要： 语音交流几乎构成了人类社会交往的方方面面，但我们几乎知道 没有关于发声器官、喉咙和声带的发育生物学。这是 一个重要的问题，因为语音问题是许多人常见但了解不多的一个方面 人类的结构性先天缺陷，以及由此带来的沟通困难，对 患者的生活质量。在这里，我们建议将小鼠作为正常和病理的模型 喉部和声带的发育。我们将系统地描述胚胎谱系和 在小鼠喉部不同组织中的基因表达模式，我们将描述 人类出生缺陷综合征小鼠模型的喉部病理发育。我们还将 用系统生物学的方法来定义哺乳动物喉部的基因调控回路 发展。通过结合遗传命运图谱、分子遗传学和系统生物学， 这里提出的实验将提供一个现代的基础，我们可以在这个基础上组装一个详细的 从机制上理解喉部发育并获得对喉癌病因的分子洞察力 人类喉部先天缺陷。

Abstract: Vocal communication underlies almost every aspect of human social interactions, yet we know almost nothing about the developmental biology of the organs of vocalization, the larynx and vocal folds. This is a significant issue because problems with voice are a common but poorly understood aspect of many human structural birth defects, and the resulting difficulty in communication has a profound effect on patients' quality of life. Here, we propose to develop the mouse as a model for normal and pathological development of the larynx and vocal folds. We will systematically characterize embryonic lineages and gene expression patterns in the diverse tissues of the mouse larynx, and we will characterize pathological laryngeal development in mouse models of human birth defect syndromes. We will also take a systems biology approach to defining gene regulatory circuitry underlying mammalian laryngeal development. By combining genetic fate mapping, molecular genetics, and systems biology, the experiments proposed here will provide a modern foundation from which we can assemble a detailed mechanistic understanding of laryngeal development and gain molecular insights into the etiology of human laryngeal birth defects.