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.
Vocal communication underlies almost every aspect of human social interactions, and while the neural basis of speech and language is intensely studied, we know almost nothing of the mechanisms underlying morphogenesis of the vocal apparatus, the organ which makes speech and language possible. This proposal seeks to fill a fundamental gap in our understanding of mammalian developmental biology by exploring the molecular genetics and morphogenesis of the mammalian larynx and vocal folds.
|Khokha, Mustafa K; Mitchell, Laura E; Wallingford, John B (2017) An opportunity to address the genetic causes of birth defects. Pediatr Res 81:282-285|
|Adler, Paul N; Wallingford, John B (2017) From Planar Cell Polarity to Ciliogenesis and Back: The Curious Tale of the PPE and CPLANE proteins. Trends Cell Biol 27:379-390|