Analysis of the molecular cascade responsible for mesodermal limb chondrogenesis:: Sox genes and BMP signaling
Analysis of the molecular cascade responsible for mesodermal limb chondrogenesis:: Sox genes and BMP signaling
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DOI：
10.1016/s0012-1606(03)00066-6
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发表时间：
2003-05-15
影响因子：
2.7
通讯作者：
Hurle, JM
中科院分区：
文献类型：
--
作者：
Chimal-Monroy, J;Rodriguez-Leon, J;Hurle, JM
在这里，我们研究了 Sox 基因和 BMP 信号在肢体软骨形成过程中如何功能耦合。使用 TGFbeta1 诱导的叉指实验模型，我们剖析了体内软骨形成过程中形态和分子事件的序列。我们的结果表明，Sox8 和 Sox9 是肢体软骨最早熟的标记物，它们的诱导是独立的，并且先于 BMP 信号传导的激活。 Sox10 似乎还与 Sox9 和 Sox8 合作建立手指软骨。此外，我们还发现，在指间中胚层中实验诱导 Sox 基因表达伴随着对外源 BMP 的细胞凋亡反应的丧失。 L-Sox5 和 Sox6 分别在软骨形成前聚集体中 Bmpr1b 表达的同时和之后被诱导，它们的激活与分化软骨中 II 型胶原蛋白和聚集蛋白聚糖基因的诱导相关。 Bmpr1b 的表达先于软骨形成前聚集体中形态变化的出现，并建立了一个里程碑，所有 Sox 基因表达的维持和软骨分化的进展变得依赖于 BMP。此外，我们发现 Ventroptin 在调节发育中的软骨中 BMP 活性方面先于 Noggin。总之，我们的研究结果表明，Sox8、Sox9 和 Sox10 具有协同功能，响应 BMP 信号赋予肢体中胚层软骨形成能力。反过来，BMP 与 Sox9、Sox6 和 L-Sox5 配合将负责软骨分化程序的执行和维护。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
Here, we have studied how Sox genes and BMP signaling are functionally coupled during limb chondrogenesis. Using the experimental model of TGFbeta1-induced interdigital digits, we dissect the sequence of morphological and molecular events during in vivo chondrogenesis. Our results show that Sox8 and Sox9 are the most precocious markers of limb cartilage, and their induction is independent and precedes the activation of BMP signaling. Sox10 appears also to cooperate with Sox9 and Sox8 in the establishment of the digit cartilages. In addition, we show that experimental induction of Sox gene expression in the interdigital mesoderm is accompanied by loss of the apoptotic response to exogenous BMPs. L-Sox5 and Sox6 are respectively induced coincident and after the expression of Bmpr1b in the prechondrogenic aggregate, and their activation correlates with the induction of Type II Collagen and Aggrecan genes in the differentiating cartilages. The expression of Bmpr1b precedes the appearance of morphological changes in the prechondrogenic aggregate and establishes a landmark from which the maintenance of the expression of all Sox genes and the progress of cartilage differentiation becomes dependent on BMPs. Moreover, we show that Ventroptin precedes Noggin in the modulation of BMP activity in the developing cartilages. In summary, our findings suggest that Sox8, Sox9, and Sox10 have a cooperative function conferring chondrogenic competence to limb mesoderm in response to BMP signals. In turn, BMPs in concert with Sox9, Sox6 and L-Sox5 would be responsible for the execution and maintenance of the cartilage differentiation program. (C) 2003 Elsevier Science (USA). All rights reserved.