Enamel Knots as Signaling Centers Linking Tooth Morphogenesis and Odontoblast Differentiation
Enamel Knots as Signaling Centers Linking Tooth Morphogenesis and Odontoblast Differentiation
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DOI：
10.1177/08959374010150010401
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发表时间：
2001-08
影响因子：
--
通讯作者：
I. Thesleff;S. Keranen;J. Jernvall
中科院分区：
文献类型：
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作者：
I. Thesleff;S. Keranen;J. Jernvall
成牙本质细胞是从牙乳头细胞分化而来的，在发育中的牙齿中，成牙本质细胞的分化是由牙齿上皮细胞诱导的。在实验研究中，没有其他间充质细胞具有分化为成牙本质细胞的能力，这表明牙乳头细胞在发育早期已致力于成牙本质细胞系。我们认为成牙本质细胞系内的提前分化是由连续的上皮信号调节的。来自早期口腔外胚层的第一批上皮信号诱导了颅神经脊细胞的成牙潜能。确定牙源性细胞谱系的下一步是从牙源性间充质中发育出牙乳头。牙乳头的形成始于牙齿形态发生从萌芽到帽状阶段的过渡阶段，这是由来自初级釉质结的上皮信号调节的。原生牙釉质结是形成于上皮牙蕾顶端的信号中心。它在帽状期的牙齿上皮细胞中充分发育和形态可辨，并表达至少10种不同的信号分子，分别属于BMP、FGF、HH和WNT家族。在磨牙中，后牙尖端的釉质上皮中会出现次生牙釉质结节。它们还表达几个信号分子，它们的形成先于上皮的折叠和生长。成牙本质细胞的分化总是从尖端开始，因此，可以想象，釉质结节中表达的一些信号可能是成牙本质细胞分化的诱导剂。不同信号在釉质结中的作用还不是很清楚。我们已经证明，FGFs刺激间充质细胞和上皮细胞的增殖，并可能调节牙尖的生长。我们已经提出，釉质结信号与间充质信号一起，在调节牙尖的图案从而调节牙冠的形状方面也具有重要的作用。我们认为釉质结是牙齿发育的中心调节器，因为它们将细胞分化与形态发生联系起来。
Odontoblasts differentiate from the cells of the dental papilla, and it has been well-established that their differentiation in developing teeth is induced by the dental epithelium. In experimental studies, no other mesenchymal cells have been shown to have the capacity to differentiate into odontoblasts, indicating that the dental papilla cells have been committed to odontoblast cell lineage during earlier developmental stages. We propose that the advancing differentiation within the odontoblast cell lineage is regulated by sequential epithelial signals. The first epithelial signals from the early oral ectoderm induce the odontogenic potential in the cranial neural crest cells. The next step in the determination of the odontogenic cell lineage is the development of the dental papilla from odontogenic mesenchyme. The formation of the dental papilla starts at the onset of the transition from the bud to the cap stage of tooth morphogenesis, and this is regulated by epithelial signals from the primary enamel knot. The primary enamel knot is a signaling center which forms at the tip of the epithelial tooth bud. It becomes fully developed and morphologically discernible in the cap-stage dental epithelium and expresses at least ten different signaling molecules belonging to the BMP, FGF, Hh, and Wnt families. In molar teeth, secondary enamel knots appear in the enamel epithelium at the sites of the future cusps. They also express several signaling molecules, and their formation precedes the folding and growth of the epithelium. The differentiation of odontoblasts always starts from the tips of the cusps, and therefore, it is conceivable that some of the signals expressed in the enamel knots may act as inducers of odontoblast differentiation. The functions of the different signals in enamel knots are not precisely known. We have shown that FGFs stimulate the proliferation of mesenchymal as well as epithelial cells, and they may also regulate the growth of the cusps. We have proposed that the enamel knot signals also have important roles, together with mesenchymal signals, in regulating the patterning of the cusps and hence the shape of the tooth crown. We suggest that the enamel knots are central regulators of tooth development, since they link cell differentiation to morphogenesis.