The expression of gsc in the region of the first pharyngeal cleft, which is where the external acoustic meatus originates, is restricted to the mesenchyme and is absent from the overlying epithelium ( Gaunt et al., 1993 also see Fig. We were interested in determining the role of gsc in morphogenesis of the tympanic membrane. Also, the bone that supports the tympanic membrane, the tympanic ring, was not present in these mutants. In these mice ( Rivera-Pérez et al., 1995 Yamada et al., 1995), the tympanic membrane did not form properly because the external acoustic meatus failed to develop. The analysis of gsc null mice indicated that expression of gsc has a role in the morphogenesis of the tympanic membrane. We observed an absolute correlation between the presence of the tympanic ring and the formation of the external acoustic meatus, suggesting that formation of the tympanic ring regulates formation and growth of the external acoustic meatus. These treatments included deletion of the tympanic ring by maternal administration of retinoic acid ( Kessel, 1992) and duplication of the tympanic ring in Hoxa-2 homozygous mutant embryos ( Gendron-Maguire et al., 1993 Rijli et al., 1993). To test this hypothesis, we analyzed formation of the external acoustic meatus in embryos where formation of the tympanic ring had been modulated experimentally.
We hypothesized that lack of formation of the external acoustic meatus in gsc null mice was causally related to lack of formation of the tympanic ring in these embryos. Histological analysis also revealed that no external acoustic meatus formed in gsc null mice ( Rivera-Pérez et al., 1995 Yamada et al., 1995). gsc null mice exhibit a deletion of the tympanic ring with complete penetrance. For example, mice homozygous for a targeted deletion of the goosecoid ( gsc) gene die perinatally with multiple craniofacial defects ( Rivera-Pérez et al., 1995 Yamada et al., 1995). Recent work using targeted mutagenesis has identified a number of genes important for craniofacial development in mice (e.g., Gendron-Maguire et al., 1993 Rijli et al., 1993 Kurihara et al., 1994 Satokata and Maas, 1994 Martin et al., 1995 Rivera-Pérez et al., 1995 Yamada et al., 1995). 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. 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 demonstrate here an absolute correlation between formation of the external acoustic meatus and formation of the tympanic ring, a first archderived membrane bone that anchors the tympanic membrane.
The other epithelial layer is contributed by the tubotympanic recess, a derivative of the first pharyngeal pouch. One epithelial layer is contributed by the external acoustic meatus, a derivative of the first pharyngeal cleft. 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.
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