Abstract
Congenital laryngeal webs result from failure of vocal fold separation during development in utero Infants present with life-threatening respiratory problems at birth, and extensive lifelong difficulties in breathing and voicing. The molecular mechanisms that instruct vocal fold formation are rarely studied. Here, we show, for the first time, that conditional inactivation of the gene encoding β-catenin in the primitive laryngopharyngeal epithelium leads to failure in separation of the vocal folds, which approximates the gross phenotype of laryngeal webbing. These defects can be traced to a series of morphogenesis defects, including delayed fusion of the epithelial lamina and formation of the laryngeal cecum, failed separation of the larynx and esophagus with reduced and disorganized cartilages and muscles. Parallel to these morphogenesis defects, inactivation of β-catenin disrupts stratification of epithelial cells and establishment of p63(+) basal progenitors. These findings provide the first line of evidence that links β-catenin function to the cell proliferation and progenitor establishment during larynx and vocal fold development.