Mechanisms of larynx and vocal fold development and pathogenesis
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Cellular and Molecular Life Sciences
REVIEW
Mechanisms of larynx and vocal fold development and pathogenesis Vlasta Lungova1 · Susan L. Thibeault1 Received: 4 December 2019 / Revised: 12 March 2020 / Accepted: 16 March 2020 © Springer Nature Switzerland AG 2020
Abstract The larynx and vocal folds sit at the crossroad between digestive and respiratory tracts and fulfill multiple functions related to breathing, protection and phonation. They develop at the head and trunk interface through a sequence of morphogenetic events that require precise temporo-spatial coordination. We are beginning to understand some of the molecular and cellular mechanisms that underlie critical processes such as specification of the laryngeal field, epithelial lamina formation and recanalization as well as the development and differentiation of mesenchymal cell populations. Nevertheless, many gaps remain in our knowledge, the filling of which is essential for understanding congenital laryngeal disorders and the evaluation and treatment approaches in human patients. This review highlights recent advances in our understanding of the laryngeal embryogenesis. Proposed genes and signaling pathways that are critical for the laryngeal development have a potential to be harnessed in the field of regenerative medicine. Keywords Laryngeal · Vocal cords · Congenital · Embryology
Introduction Voice problems occur in between 3 and 9% of the population in the United States [78]. Although a majority of these problems arise due to vocal fold (VF) structural and neurologic abnormalities, phonotrauma and/or laryngeal inflammation [38], there is a clear segment of the population in which voice disorders develop secondary to defects that occur during intrauterine development [11]. These congenital voice disorders can be caused by a wide variety of abnormalities along the aerodigestive tract, including larynx and vocal folds (VF). Molecular and cellular mechanisms that control formation of laryngeal structures are beginning to be elucidated, but we are still far behind the research that has been done in upper airways or lungs [36, 61]. Frequently used animal models, such as felines, non-human primates, canines, pigs, rabbits or rats allow for the examination of laryngeal biology and testing of broad arrays of medical, surgical and behavioral interventions [3, 10, 12, 17, 30, 54, 77, 89]; however, these animal models have limitations for studying epithelio-mesenchymal interactions in genetically * Susan L. Thibeault [email protected] 1
linked diseases related to laryngeal development and/or regeneration. The recent introduction and use of transgenic mice in voice research should significantly improve our understanding of normal laryngeal cell biology and genetically linked disease processes. Basic research into the mechanisms controlling laryngeal morphogenesis is important for a number of reasons. First, congenital laryngeal defects are potentially life-threatening at birth, as they can be accompanied with airway obstruction, and can cause pro
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