Regulation of skeletogenic differentiation in cranial dermal bone
Regulation of skeletogenic differentiation in cranial dermal bone
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DOI：
10.1242/dev.002709
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发表时间：
2007-09-01
期刊：
影响因子：
4.6
通讯作者：
Tabin, Clifford J.
中科院分区：
文献类型：
--
作者：
Abzhanov, Arhat;Rodda, Stephen J.;Tabin, Clifford J.
尽管四肢和中轴骨骼的软骨内骨化相对较好地理解，但以许多颅面骨骼元素为特征的真皮（膜内）骨的发育还没有得到很好的描述。我们分析了许多先前与软骨内骨骼发育相关的标记物的表达域，以定义参与鸡和小鼠真皮骨化过程的细胞转变。这导致人们认识到真皮分化途径中的一系列不同步骤，包括以成骨和软骨形成标记物表达为特征的独特细胞类型。发现先前与软骨内发育有关的几种信号分子在真皮骨形成的特定阶段表达。使用逆转录病毒错误表达对其中三个进行了功能研究。我们发现骨形态发生蛋白（BMP）的活性是神经嵴来源的间充质参与成骨途径所必需的，并且印度刺猬蛋白（IHH）和甲状旁腺激素相关蛋白（PTHrP，PTHLH）负向调节从前成骨细胞祖细胞到成骨细胞的转变。这些结果为理解真皮骨发育提供了一个框架，旨在使其更接近软骨内骨发育可用的分子和细胞分辨率。
Although endochondral ossification of the limb and axial skeleton is relatively well-understood, the development of dermal ( intramembranous) bone featured by many craniofacial skeletal elements is not nearly as well-characterized. We analyzed the expression domains of a number of markers that have previously been associated with endochondral skeleton development to define the cellular transitions involved in the dermal ossification process in both chick and mouse. This led to the recognition of a series of distinct steps in the dermal differentiation pathways, including a unique cell type characterized by the expression of both osteogenic and chondrogenic markers. Several signaling molecules previously implicated in endochondrial development were found to be expressed during specific stages of dermal bone formation. Three of these were studied functionally using retroviral misexpression. We found that activity of bone morphogenic proteins (BMPs) is required for neural crest-derived mesenchyme to commit to the osteogenic pathway and that both Indian hedgehog (IHH) and parathyroid hormone-related protein (PTHrP, PTHLH) negatively regulate the transition from preosteoblastic progenitors to osteoblasts. These results provide a framework for understanding dermal bone development with an aim of bringing it closer to the molecular and cellular resolution available for the endochondral bone development.