Visualization of cartilage formation: Insight into cellular properties of skeletal progenitors and chondrodysplasia syndromes
Visualization of cartilage formation: Insight into cellular properties of skeletal progenitors and chondrodysplasia syndromes
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DOI：
10.1016/j.devcel.2007.04.016
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发表时间：
2007-06-01
影响因子：
11.8
通讯作者：
Niswander, Lee
中科院分区：
文献类型：
--
作者：
Barna, Maria;Niswander, Lee
骨骼形态发生和软骨模板形成的细胞事件在很大程度上是未知的。我们生成了一个成像系统，动态可视化四肢间充质细胞经历连续阶段的软骨形成，并描绘软骨发育不良综合征中发现突变的软骨形成的关键调节因子的细胞功能。我们发现了Sox 9在控制细胞形态方面的一个意料之外的作用，独立于其主要下游靶点Collia，这是间充质向软骨细胞转变所必需的。相反，Bmp信号调节细胞程序，我们称之为“压实”，其中间充质细胞获得描绘软骨元件的边界和大小所需的粘性细胞行为。此外，我们可视化了来自肢芽不同区域的标记祖细胞，并确定了独特的细胞特性，这些特性可能会引导它们对特定骨骼元素（如肱骨或手指）的贡献。这些发现揭示了软骨发育不良综合征和脊椎动物骨骼形成的细胞基础。
The cellular events underlying skeletal morphogenesis and the formation of cartilage templates are largely unknown. We generated an imaging system to dynamically visualize limb mesenchymal cells undergoing successive phases in cartilage formation and to delineate the cellular function of key regulators of chondrogenesis found mutated in chondrodysplasia syndromes. We uncovered an unsuspected role for Sox9 in control of cell morphology, independent from its major downstream target Collia, critically required for the mesenchyme-to-chondrocyte transition. In contrast, Bmp signaling regulates a cellular program we term "compaction" in which mesenchymal cells acquire a cohesive cell behavior required to delineate the boundaries and size of cartilage elements. Moreover, we visualized labeled progenitor cells from different regions of the limb bud and identified unique cellular properties that may direct their contribution toward specific skeletal elements such as the humerus or digits. These findings shed light on the cellular basis for chondrodysplasia syndromes and formation of the vertebrate skeleton.