BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development.
BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development.
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DOI：
10.1242/dev.127.21.4711
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发表时间：
2000-11
期刊：
影响因子：
4.6
通讯作者：
M. Bei;K. Kratochwil;R. Maas
中科院分区：
文献类型：
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作者：
M. Bei;K. Kratochwil;R. Maas
许多器官的发育依赖于连续的上皮-间充质相互作用，发育中的牙胚为阐明这些诱导组织相互作用的性质提供了一个强有力的模型。在Msx1缺陷型小鼠中，牙齿发育在芽期停止，此时需要Msx1来表达牙齿间充质中的Bmp4和Fgf3（Bei，M.和Maas，R.（1998）Development 125，4325 - 4333）。为了确定Msx1功能的组织要求，我们进行了野生型和Msx1突变牙上皮和间充质之间的组织重组。我们表明，通过E14.5帽阶段的牙齿发育，Msx1是牙齿形成所需的牙齿间充质。帽阶段后，然而，牙齿发育成为Msx1独立的，虽然我们的实验确定了进一步的后期功能Msx1在成牙本质细胞和牙髓生存。这些结果表明，在帽阶段之前，牙上皮从牙齿形成所必需的牙间充质接收Msx1依赖性信号。为了进一步验证这一假设，首先将Msx1突变牙胚与BMP 4或各种FGF在体外培养两天，然后在同基因小鼠的肾包膜下生长，以完成器官发生和终末分化。先前，使用体外培养系统，我们显示BMP 4刺激Msx 1突变牙上皮的生长（Chen，Y.，Bei，M.喔，我，萨托卡塔岛和Maas，R.（1996年）。Development 122，3035 - 3044）。使用更强大的肾包膜移植程序，我们现在表明，当在移植前添加到Msx1缺陷的牙胚中时，BMP 4可以拯救Msx1突变的牙胚，直到牙釉质和牙本质形成的最终阶段。总的来说，这些结果建立了牙齿间充质中Msx 1的短暂功能需求，其几乎完全由BMP 4单独提供，而不是FGF。此外，他们正式证明了BMP 4与Msx1的下游关系，建立了牙齿发生过程中Msx1的非细胞自主性质，并公开了Msx1在成牙本质细胞和牙髓中的额外晚期存活功能。
The development of many organs depends on sequential epithelial-mesenchymal interactions, and the developing tooth germ provides a powerful model for elucidating the nature of these inductive tissue interactions. In Msx1-deficient mice, tooth development arrests at the bud stage when Msx1 is required for the expression of Bmp4 and Fgf3 in the dental mesenchyme (Bei, M. and Maas, R. (1998) Development 125, 4325-4333). To define the tissue requirements for Msx1 function, we performed tissue recombinations between wild-type and Msx1 mutant dental epithelium and mesenchyme. We show that through the E14.5 cap stage of tooth development, Msx1 is required in the dental mesenchyme for tooth formation. After the cap stage, however, tooth development becomes Msx1 independent, although our experiments identify a further late function of Msx1 in odontoblast and dental pulp survival. These results suggest that prior to the cap stage, the dental epithelium receives an Msx1-dependent signal from the dental mesenchyme that is necessary for tooth formation. To further test this hypothesis, Msx1 mutant tooth germs were first cultured with either BMP4 or with various FGFs for two days in vitro and then grown under the kidney capsule of syngeneic mice to permit completion of organogenesis and terminal differentiation. Previously, using an in vitro culture system, we showed that BMP4 stimulated the growth of Msx1 mutant dental epithelium (Chen, Y., Bei, M. Woo, I., Satokata, I. and Maas, R. (1996). Development 122, 3035-3044). Using the more powerful kidney capsule grafting procedure, we now show that when added to explanted Msx1-deficient tooth germs prior to grafting, BMP4 rescues Msx1 mutant tooth germs all the way to definitive stages of enamel and dentin formation. Collectively, these results establish a transient functional requirement for Msx1 in the dental mesenchyme that is almost fully supplied by BMP4 alone, and not by FGFs. In addition, they formally prove the postulated downstream relationship of BMP4 with respect to Msx1, establish the non-cell-autonomous nature of Msx1 during odontogenesis, and disclose an additional late survival function for Msx1 in odontoblasts and dental pulp.