Partanen A M, Thesleff I
Dev Biol. 1987 Mar;120(1):186-97. doi: 10.1016/0012-1606(87)90117-5.
We have shown earlier that epidermal growth factor (EGF) inhibits morphogenesis and cell differentiation in mouse embryonic teeth in organ culture. This inhibition depends on the stage of tooth development so that only teeth at early developmental stages respond to EGF (A-M. Partanen, P. Ekblom, and I. Thesleff (1985) Dev. Biol. 111, 84-94). We have now studied the quantity and pattern of EGF binding in teeth at various stages of development by incubating the dissected tooth germs with 125I-labeled EGF. Although the quantity of 125I-EGF binding per microgram DNA stays at the same level, localization of 125I-EGF binding by autoradiography reveals that the distribution of binding sites changes dramatically. In bud stage the epithelial tooth bud that is intruding into the underlying mesenchyme has binding sites for EGF, but the condensation of dental mesenchymal cells around the bud does not bind EGF. At the cap stage of development the dental mesenchyme binds EGF, but the dental epithelium shows no binding. This indicates that the dental mesenchyme is the primary target tissue for the inhibitory effect of EGF on tooth morphogenesis during early cap stage. During advanced morphogenesis the binding sites of EGF disappear also from the dental papilla mesenchyme, but the dental follicle which consists of condensed mesenchymal cells surrounding the tooth germ, binds EGF abundantly. We have also studied EGF binding during the development of other embryonic organs, kidney, salivary gland, lung, and skin, which are all formed by mesenchymal and epithelial components. The patterns of EGF binding in various tissues suggest that EGF may have a role in the organogenesis of epitheliomesenchymal organs as a stimulator of epithelial proliferation during initial epithelial bud formation and branching morphogenesis. The results of this study indicate that EGF stimulates or maintains proliferation of undifferentiated cells during embryonic development and that the expression of EGF receptors in different organs is not related to the age of the embryo, but is specific to the developmental stage of each organ.
我们之前已经表明，表皮生长因子（EGF）在器官培养中会抑制小鼠胚胎牙齿的形态发生和细胞分化。这种抑制作用取决于牙齿发育的阶段，因此只有处于早期发育阶段的牙齿才会对EGF产生反应（A - M. 帕尔塔宁、P. 埃克布洛姆和I. 泰斯莱夫（1985年）《发育生物学》111卷，84 - 94页）。我们现在通过用125I标记的EGF孵育解剖后的牙胚，研究了处于不同发育阶段的牙齿中EGF结合的数量和模式。尽管每微克DNA上125I - EGF结合的数量保持在相同水平，但通过放射自显影对125I - EGF结合的定位显示，结合位点的分布发生了显著变化。在芽期，侵入下方间充质的上皮牙芽有EGF的结合位点，但围绕牙芽的牙间充质细胞凝聚物不结合EGF。在发育的帽期，牙间充质结合EGF，但牙上皮无结合。这表明在帽期早期，牙间充质是EGF对牙齿形态发生抑制作用的主要靶组织。在高级形态发生过程中，EGF的结合位点也从牙乳头间充质消失，但由围绕牙胚的凝聚间充质细胞组成的牙囊大量结合EGF。我们还研究了其他胚胎器官，如肾脏、唾液腺、肺和皮肤在发育过程中的EGF结合情况，这些器官均由间充质和上皮成分构成。不同组织中EGF结合的模式表明，EGF可能在上皮 - 间充质器官的器官发生中起作用，作为初始上皮芽形成和分支形态发生过程中上皮增殖的刺激因子。这项研究的结果表明，EGF在胚胎发育过程中刺激或维持未分化细胞的增殖，并且不同器官中EGF受体的表达与胚胎年龄无关，而是特定于每个器官的发育阶段。
