Hedgehog signaling is essential to maintain epithelial identity during larynx and foregut morphogenesis.

Purpose: This study seeks to determine the role of Hedgehog signaling in larynx development. Methods: To determine how Hedgehog signaling directs larynx epithelial morphogenesis we used genomic approaches to identify a novel set of Hedgehog target genes within the early larynx. To this end, we performed bulk RNA-seq on 3-pooled E10.5 (32-35S) larynx tissues from wild-type (2 replicates) and Shh-/- (2 replicates) embryos. From this experiment we identified 1873 differentially expressed genes (p-value <0.05). Results: Hedgehog is essential for maintaining the identity of foregut-derived epithelial cells within the larynx vocal folds. In the absence of HH signaling these epithelial cells undergo specific transcriptional changes to initiate a partial epithelial-to-mesenchymal transition, migrate out of the epithelial layer and under go cell death. The layer is then replaced by a different population of cells. Overall design: Bulk RNA-seq on 3-pooled E10.5 larynx tissues in wild-type and Shh-/- embryos (32-35S).