1: Dentin Pulp Complex: Proceeding of the International Conference on Dentin Pulp Complex 2001. 2001 in press.

Functional significance of Msx2 gene during tooth development.

Ohshima H, Maeda T, Maas R, Satokata I.

Division of Oral Anatomy, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori, Japan. histoman@dent.niigata-u.ac.jp

During tooth development, the expression of Msx2 mRNA is spatiotemporally shifted among the several components of the dental epithelium and mesenchyme (Mackenzie et al. Development 115:403-420, 1992). Recently, we demonstrated that Msx2-deficient mice displayed defective tooth, hair follicle and mammary gland development, in addition to defects of skull ossification and persistent calvarial foramen (Satokata et al. Nat. Genet. 24:391-395, 2000). Although Msx2-deficient mice have shown the abnormalities of amelogenesis, the detailed phenotypes remain to be clarified. The present study analyzed on the abnormalities of tooth development in Msx2-deficient mice. The phenotypes of defective teeth observed in the Msx2^-/- mice were as follows: 1) The enamel organ showed condensed features preventing the vascular invasion there to induce the TUNEL-negative degeneration of ameloblasts. 2) Secretory ameloblasts represented abnormal features such as irregular shaped Tomes' processes and numerous vacuoles in their distal cytoplasm. 3) The enamel organ contained no TUNEL-positive cells, although the temporary appearance of TUNEL-positive cells occurred in the wild type mice. 4) Both crown and root in the Msx2^-/- mice showed the irregular-shaped morphology, concomitant with the abnormal development of Hertwig's epithelial root sheath. 5) The amelogenesis imperfecta was caused by the degeneration of ameloblasts and by the disappearance of enamel free area in the cusped area of molar teeth. Our results in this study provided evidence that Msx2 plays crucial roles in amelogenesis and the normal morphology of the tooth.

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