Threshold-specific requirements for Bmp4 in mandibular development
Threshold-specific requirements for Bmp4 in mandibular development
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DOI：
10.1016/j.ydbio.2005.04.019
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发表时间：
2005-07-15
影响因子：
2.7
通讯作者：
Martin, JF
中科院分区：
文献类型：
--
作者：
Liu, W;Selever, J;Martin, JF
下颌骨的发育是由特定的鳃弓外胚层和塑料间充质之间的相互作用来调节的。此外，来自咽内胚层的信号已被证明是重要的下颌骨形态发生。为了深入了解下颌骨形态的调控机制，研究上皮源性信号的功能具有重要意义。BMP 4在下颌弓远端外胚层和咽内胚层均有表达。在这里，我们表明，Bmp4在下颌骨外胚层和在较小程度上在咽内胚层的缺失，导致下颌骨发育的严重缺陷。此外，我们的数据揭示了不同的Bmp4阈值表达的BMP依赖Msx1和Msx2基因在下颌骨间充质。我们还发现，外胚层Fgf8的表达被激活和抑制Bmp4在一个剂量依赖性的方式表明一个新的Bmp4功能的阈值特异性调节铁转录。最后，我们提供的证据表明，Prx同源框基因抑制Msx2转基因的表达，以前被证明是Bmp4响应，揭示了Msx1和Msx2的Pmp信号的差异调节机制。(c)2005年爱思唯尔公司All rights reserved.
Mandibular development is regulated by an interplay between a specified branchial arch ectoderm and a plastic mesenchyme. Moreover, signaling from the pharyngeal endoderm has been shown to be important for mandibular morphogenesis. To gain insight into the mechanisms regulating mandibular pattern, it is important to investigate the function of the epithelial-derived signals. Bmp4 is expressed in both distal, mandibular arch ectoderm and pharyngeal endoderm. Here, we show that deletion of Bmp4 in the mandibular ectoderm and to a lesser extent in the pharyngeal endoderm, resulted in severe defects in mandibular development. Furthermore, our data uncovered different Bmp4 thresholds for expression of the Bmp-dependent Msx1 and Msx2 genes in mandibular mesenchyme. We also found that ectodermal Fgf8 expression was both activated and repressed by Bmp4 in a dosage-dependent fashion indicating a novel Bmp4 function in threshold-specific regulation of Fe transcription. Lastly, we provide evidence that Prx homeobox genes repress expression of an Msx2 transgene, previously shown to be Bmp4-responsive, revealing a mechanism for differential regulation of Msx1 and Msx2 by Pmp signaling. (c) 2005 Elsevier Inc. All rights reserved.