Development of the mammalian ear: coordinate regulation of formation of the tympanic ring and the external acoustic meatus.

The tympanic membrane in mammals is a trilaminar structure formed by the apposition of two epithelial cell layers, along with an intervening layer of cells derived from pharyngeal arch mesenchyme. One epithelial layer is contributed by the external acoustic meatus, a derivative of the first pharyngeal cleft. The other epithelial layer is contributed by the tubotympanic recess, a derivative of the first pharyngeal pouch. We demonstrate here an absolute correlation between formation of the external acoustic meatus and formation of the tympanic ring, a first arch-derived membrane bone that anchors the tympanic membrane. Experimental loss of the tympanic ring by retinoic acid treatment, or duplication of the ring in Hoxa-2 null mutant embryos, resulted in corresponding alterations in formation of the external acoustic meatus. We suggest that the tympanic ring primordium induces formation and morphogenesis of the external acoustic meatus, and that expression of the Hoxa-2 and goosecoid genes may be involved in regulating the formation and morphogenesis of these structures.