Role of Islet1 in the patterning of murine dentition
Role of Islet1 in the patterning of murine dentition
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DOI：
10.1242/dev.00631
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发表时间：
2003-09-01
期刊：
影响因子：
4.6
通讯作者：
Sharpe, PT
中科院分区：
文献类型：
--
作者：
Mitsiadis, TA;Angeli, I;Sharpe, PT
据信，小鼠的齿系是由口腔上皮预先形成臼齿（近端）和切牙（远端）区域的图案决定的。LIM同源结构域蛋白Isletl（ISL 1）参与调节许多细胞类型和器官的分化。在牙形成过程中，我们发现Islet 1只在发育中的切牙上皮细胞中表达，但在磨牙发育过程中不表达。Islet 1在推定切牙上皮中的早期表达与Bmp 4的表达一致，Bmp 4的作用是诱导Msx 1在下层间充质中的表达。在切牙形状的获得中，我们分析了Islet 1在下颌外植体中表达的调节。局部应用骨形态发生蛋白4（BMP 4）在磨牙区的上皮细胞通过珠粒植入或电穿孔刺激Islet 1的表达。用头蛋白抑制BMP信号传导导致Islet 1表达的丧失。在远端上皮中抑制Islet 1导致Bmp 4表达的丧失和相应的Msx 1表达的丧失，表明在远端上皮中ISL 1和BMP 4之间存在正调控环。近端上皮中Islet 1的异位表达导致间充质中Barx 1表达的丧失，并导致磨牙发育的抑制。使用上皮/间充质重组，我们表明，在E10.5胰岛1的表达是独立的基础间充质，而在E12.5时，牙齿形状规格已通过间充质，胰岛1的表达需要远端（推定门齿）间充质。因此，Islet 1在调节颌骨和牙齿发育过程中的远端基因表达中起着重要作用。
It is believed that mouse dentition is determined by a prepatterning of the oral epithelium into molar (proximal) and incisor (distal) regions. The LIM homeodomain protein Isletl (ISL1) is involved in the regulation of differentiation of many cell types and organs. During odontogenesis, we find Islet1 to be exclusively expressed in epithelial cells of the developing incisors but not during molar development. Early expression of Islet1 in presumptive incisor epithelium is coincident with expression of Bmp4, which acts to induce Msx1 expression in the underlying mesenchyme.To define the role of ISL1. in the acquisition of incisor shape, we have analysed regulation of Islet1 expression in mandibular explants. Local application of bone morphogenetic protein 4 (BMP4) in the epithelium of molar territories either by bead implantation or by electroporation stimulated Islet1 expression. Inhibition of BMP signalling with Noggin resulted in a loss of Islet1 expression. Inhibition of Islet1 in distal epithelium resulted in a loss of Bmp4 expression and a corresponding loss of Msx1 expression, indicating that a positive regulatory loop exists between ISL1 and BMP4 in distal epithelium. Ectopic expression of Islet1 in proximal epithelium produces a loss of Barx1 expression in the mesenchyme and resulted in inhibition of molar tooth development. Using epithelial/mesenchymal recombinations we show that at E10.5 Islet1 expression is independent of the underlying mesenchyme whereas at E12.5 when tooth shape specification has passed to the mesenchyme, Islet1 expression requires distal (presumptive incisor) mesenchyme. Islet1 thus plays an important role in regulating distal gene expression during jaw and tooth development.