Study on the function of Tabby gene in tooth development

虎斑鼠是一种小鼠突变体，其特征是外胚层器官发育缺陷：牙齿、毛发和一部分腺体。外胞质异常蛋白（Ectodysplasin）是一种由虎斑猫基因编码的蛋白，最近被发现是一种新的类似tnf的跨膜蛋白，但对其功能知之甚少。通过对成年牙和胚胎牙的分析，详细研究了虎斑牙的表型。虎斑第一磨牙牙尖数目减少，颊尖与舌尖衔接，牙尖形态缺损明显。发育障碍首先在萌芽期臼齿形态上可见。帽期虎斑牙的初级牙釉质结表达了所分析的所有牙釉质结标记，但比野生型小，第一对正在发育的次级牙釉质结融合。我们认为虎斑牙的表型是由于发育早期的生长迟缓，导致初级牙釉质结的信号减少，随后是牙上皮生长不足，缺乏最后发育的次级牙釉质结的形成。外质异常蛋白转录本在牙釉质上皮和牙板中表达。在离体培养时，虎斑花蕾/帽期磨牙形成的尖牙比野生型对照少。尽管之前提出了虎斑猫和EGF之间的联系，但外源添加的EGF并没有挽救这种表型。相反，FGF-10部分恢复了虎斑磨牙的形态发生，并刺激了额外牙尖的发育。

Tabby is a mouse mutant characterized by deficient development of the ectodermal organs : teeth, hair, and a subset of glands. Ectodysplasin, the protein encoded by the Tabby gene, was recently identified as a novel TNF-like transmembrane protein but little is known about its function. We have examined the Tabby tooth phenotype in detail by analysis of the adult and embryonic teeth. Tabby first molars had an obvious defect in cusp patterning as the number of cusps was reduced and the buccal and lingual cusps were joined. The disturbance in development was first visible morphologically in the bud 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 first pair of developing secondary enamel knots was fused. We propose that the 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 formation of the last developing secondary enamel knots. The ectodysplasin transcripts were expressed in the outer enamel epithelium and dental lamina. When cultured in vitro Tabby bud/cap stage molars formed fewer cusps than wild-type controls. This phenotype was not rescued by exogenously added EGF despite the previously proposed link between Tabby and EGF.Instead FGF-10 partially restored morphogenesis and stimulated the development of additional tooth cusps in cultured Tabby molars.