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Development of the middle ear has been the subject of competing hypotheses. Thompson and Tucker (p. 1453; see the Perspective by Fekete and Noden) used transgenic mice to follow the cell types that form the middle ear. During development of the middle ear, a balloon of endoderm expands that bursts, allowing entry of mesenchymal neural crest cells. As the mesenchyme withdraws, a cavity is formed, partly lined with remnants of the endodermal balloon. The mature middle ear in mouse is thus lined partly by endoderm, with its rich ciliation typical of mucosal epithelia, and in part by neural crest cells, which lack cilia.
The air-filled cavity and ossicles of the mammalian middle ear conduct sound to the cochlea. Using transgenic mice, we show that the mammalian middle ear develops through cavitation of a neural crest mass. These cells, which previously underwent an epithelial-to-mesenchymal transformation upon leaving the neural tube, undergo a mesenchymal-to-epithelial transformation to form a lining continuous with the endodermally derived auditory tube. The epithelium derived from endodermal cells, which surrounds the auditory tube and eardrum, develops cilia, whereas the neural crest–derived epithelium does not. Thus, the cilia critical to clearing pathogenic infections from the middle ear are distributed according to developmental derivations. A different process of cavitation appears evident in birds and reptiles, indicating that this dual epithelium may be unique to mammals.