Molecular genetics of mammalian larynx and vocal fold development

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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.