Gli3 and the developmental biology of the mammalian voice
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Vocal communication is essential to human behavior, but the developmental biology of the larynx is largely unexplored. Many human congenital syndromes present with laryngeal malformations as well as voice defects including Greig cephalopolysyndactyly (GCPS) patients (Sataloff et al., 1995; Papay & Arnold, 2002). GCPS is caused by null mutations and deletions in the Gli3 gene, a member of the hedgehog signaling pathway (Hui & Joyner, 1993; Johnson, 1967). Loss of Gli3 is often associated with catastrophic changes in neural crest-derived structures in face and skull (XXX). In this study, we aim to shed light on the development of the larynx, the origins of laryngeal tissues, and the role of Gli3 in the development of the neural crest-derived laryngeal components. Here we show that the thyroid cartilage and vocal ligament are derived from the neural crest whereas the other laryngeal cartilages and musculature are mesoderm-derived. We characterize molecular markers for various tissue types in the larynx including muscle, cartilage, neurons, and vocal ligament. We used the Gli3 null mouse to understand the role of Gli3 in laryngeal development and to better understand how congenital malformations of the larynx affect vocalizations. In Gli3 [superscript xt/xt] null embryos, we detected the increase of neural crest-derived vocal ligament tissue at the expense of the thyroarytenoid muscle and the glottic opening. Finally, we detected a vocal phenotype consisting of changes in bandwidth and amplitude when comparing Gli3 [superscript +/xt] pups and their wild type littermates.