Formation of the middle ear: Recent progress on the developmental and molecular mechanisms

The middle ear allows animals to hear while moving in an aerial medium. It is composed of a cavity harbouring a chain of three ossicles that transmit vibrations produced by airborne sound in the tympanic membrane into the inn er ear, where they are converted into neural impulses. The middle ear devel ops in the branchial arches, and this requires sequential interactions betw een the epithelia and the underlying mesenchyme. Gene-inactivation experime nts have identified genes required for the formation of different middle ea r components. Some encode for signalling molecules, including Endothelin1 a nd Egf8, probable mediators of epithelial-mesenchymal interactions. Other g enes, including Eya1, Prx1, Hoxa1, Hoxa2, D1x1, D1x2, D1x5, and Gsc, are mo st likely involved in patterning and morphogenetic processes in the neural crest-derived mesenchyme. Mechanisms controlling formation of a functional tympanic membrane are also discussed. Basically, the tympanic ring, which s erves as support for the tympanic membrane, directs invagination of the fir st pharingeal cleft ectoderm to form the external acoustic meatus (EAM), wh ich provides the outer layer of the membrane. Gsc and Prx1 are essential fo r tympanic ring development. While invaginating, the EAM controls skeletoge nesis in the underlying mesenchyme to form the manubrium of the malleus, th e link between the membrane and the middle ear ossicles. (C) 2001 Academic Press.