Joint Development Involves a Continuous Influx of Gdf5-Positive Cells.
Joint Development Involves a Continuous Influx of Gdf5-Positive Cells.
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DOI：
10.1016/j.celrep.2016.05.055
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发表时间：
2016-06-21
期刊：
影响因子：
8.8
通讯作者：
Zelzer E
中科院分区：
文献类型：
--
作者：
Shwartz Y;Viukov S;Krief S;Zelzer E
滑膜关节包括几种组织类型，包括关节软骨、关节囊和韧带。所有这些区室通常被认为起源于一组早期表达gdf5的祖细胞，这些祖细胞位于区间结构域。在这里，我们提供的证据表明，关节的发育是通过细胞不断流入关节间区，在那里它们对形成关节组织有不同的贡献。使用敲入Gdf5-CreERT2小鼠，我们发现早期标记gdf5阳性区间细胞未能标记整个器官。相反，多个Cre激活步骤表明这些细胞在发育后期对各种关节室有贡献。Gdf5和tdTomato报告基因表达的时空差异支持了持续招募过程的概念。最后，Gdf5阳性细胞对不同组织的不同贡献表明，Gdf5表达的时空动态可能指导谱系分化。这项工作支持了联合发展的流入模型，该模型可能适用于其他有机成因过程。滑膜关节的发育涉及细胞持续流入区间Gdf5阳性区间细胞对不同关节组织的贡献不同，Gdf5表达的复杂时空动态可能指导谱系分化，该流入模型扩展了当前关节发育的观点，认为滑膜关节起源于一组早期指定的祖细胞。Shwartz等人使用敲入Gdf5-CreERT2的小鼠，表明关节是通过细胞不断流入区间而发育的。Gdf5表达的复杂时空动态可能揭示了谱系分化的机制。
Synovial joints comprise several tissue types, including articular cartilage, the capsule, and ligaments. All of these compartments are commonly assumed to originate from an early set of Gdf5-expressing progenitors populating the interzone domain. Here, we provide evidence that joints develop through a continuous influx of cells into the interzone, where they contribute differentially to forming joint tissues. Using a knockin Gdf5-CreERT2 mouse, we show that early labeling of Gdf5-positive interzone cells failed to mark the entire organ. Conversely, multiple Cre activation steps indicated a contribution of these cells to various joint compartments later in development. Spatiotemporal differences between Gdf5 and tdTomato reporter expression support the notion of a continuous recruitment process. Finally, differential contribution of Gdf5-positive cells to various tissues suggests that the spatiotemporal dynamics of Gdf5 expression may instruct lineage divergence. This work supports the influx model of joint development, which may apply to other organogenic processes. Synovial joint development involves a continuous influx of cells into the interzone Gdf5-positive interzone cells contribute differentially to various joint tissues The complex spatiotemporal dynamics of Gdf5 expression may instruct lineage divergence The influx model expands the current view of joint development Synovial joints are assumed to originate from a set of early-specified progenitors. Using a knockin Gdf5-CreERT2 mouse, Shwartz et al. show that joints develop through a continuous influx of cells into the interzone. The complex spatiotemporal dynamics of Gdf5 expression may reveal a mechanism of lineage divergence.