Cusp patterning defect in Tabby mouse teeth and its partial rescue by FGF

Tabby is a mouse mutant characterized by deficient development of the ectod ermal organs: teeth, hair, and a subset of glands. Ectodysplasin, the prote in encoded by the Tabby gene, was recently identified as a novel TNF-like t ransmembrane protein but little is known about its function. We have examin ed the Tabby tooth phenotype in detail by analysis of the adult and embryon ic teeth. Tabby first molars had an obvious defect in cusp patterning as th e number of cusps was reduced and the buccal and lingual cusps were joined. The disturbance in development was first visible morphologically in the bu d stage molar. The primary enamel knot in a cap stage Tabby tooth expressed all enamel knot markers analyzed but was smaller than wild type and the fi rst pair of developing secondary enamel knots was fused. We propose that th e Tabby tooth phenotype is due to growth retardation during early stages of development which leads to reduced signaling from the primary enamel knot, followed by deficient growth of the dental epithelium and lack of formatio n of the last developing secondary enamel knots. The ectodysplasin transcri pts were expressed in the outer enamel epithelium and dental lamina. When c ultured in vitro Tabby bud/cap stage molars formed fewer cusps than wild-ty pe controls. This phenotype was not rescued by exogenously added EGF despit e the previously proposed link between Tabby and EGF. Instead FGF-10 partia lly restored morphogenesis and stimulated the development of additional too th cusps in cultured Tabby molars. (C) 1999 Academic Press.