Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture inesenchyme
Dlx5 drives Runx2 expression and osteogenic differentiation in developing cranial suture inesenchyme
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DOI：
10.1016/j.ydbio.2007.01.003
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发表时间：
2007-04-15
影响因子：
2.7
通讯作者：
Monsoro-Burq, Anne-Helene
中科院分区：
文献类型：
--
作者：
Holleville, Nicolas;Mateos, Stephanie;Monsoro-Burq, Anne-Helene
颅面骨来源于头神经嵴，通过软骨内骨化或膜内骨化。在这里，我们解决的作用，同源框转录因子Dlx5在颅骨膜分化的初始步骤，我们表明，Dlx5 elaborate Runx2诱导和完整的成骨细胞分化的胚胎缝间充质生长“在体外”。首先，我们比较了Dlx5的表达，骨相关基因的表达在发展中的头骨和下颌骨。我们将基因分为与骨化的连续步骤相关的三组。其次，我们研究了Dlx5在成骨细胞前体中的活性，通过将Dlx5插入在Dlx5和Runx2表达或骨生成开始之前解剖的颅骨间充质中。我们发现，Dlx5不修改未成熟的颅骨细胞的增殖率或缝合标记的表达。相反，Dlx5通过触发Runx2、骨桥蛋白、碱性磷酸酶和其他基因表达，在这些早期原代细胞中启动完全的成骨分化，所述基因表达根据在颅骨成骨“体内”期间观察到的连续时间序列。第三，我们表明，BMP信号激活Dlx 5，Runx2，和碱性磷酸酶在这些原代培养和显性负Dlx因子干扰的BNIP途径的能力，激活Runx2的表达。总之，这些数据表明Dlx 5和相关Dlx因子在分化的发生中的关键作用。鸡头盖骨成骨细胞的细胞。(c)2007年爱思唯尔公司All rights reserved.
Cramofacial bones derive from cephalic neural crest, by endochondral or intramembranous ossification. Here, we address the role of the homeobox transcription factor Dlx5 during the initial steps of calvaria membranous differentiation and we show that Dlx5 elicits Runx2 induction and full osteoblast differentiation in embryonic suture mesenchyme grown "in vitro". First, we compare Dlx5 expression to bone-related gene expression in the developing skull and mandibular bones. We classify genes into three groups related to consecutive steps of ossification. Secondly, we study Dlx5 activity in osteoblast precursors, by transfecting Dlx5 into skull mesenchyme dissected prior to the onset of either Dlx5 and Runx2 expression or osteogenesis. We find that Dlx5 does not modify the proliferation rate or the expression of suture markers in the immature calvaria cells. Rather, Dlx5 initiates a complete osteogenic differentiation in these early primary cells, by triggering Runx2, osteopontin, alkaline phosphatase, and other gene expression according to the sequential temporal sequence observed during skull osteogenesis "in vivo". Thirdly, we show that BMP signaling activates Dlx5, Runx2, and alkaline phosphatase in those primary cultures and that a dominant-negative Dlx factor interferes with the ability of the BNIP pathway to activate Runx2 expression. Together, these data suggest a pivotal role of Dlx5 and related Dlx factors in the onset of differentiation. of chick calvaria osteoblasts. (c) 2007 Elsevier Inc. All rights reserved.