Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo.
Ectodermal Wnt6 is an early negative regulator of limb chondrogenesis in the chicken embryo.
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DOI：
10.1186/1471-213x-10-32
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发表时间：
2010-03-25
影响因子：
--
通讯作者：
Scaal M
中科院分区：
文献类型：
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作者：
Geetha-Loganathan P;Nimmagadda S;Christ B;Huang R;Scaal M
肢体骨骼的模式形成受到位于肢体原基的外胚层鞘和间质核心的信号中心复杂的相互作用的调节，从而在前肢形成肱骨、桡骨、尺骨、腕骨、掌骨和手指的坐标阵列。鲜为人知的是，为什么骨骼成分仅在肢体的中央间充质中形成，而肌肉原基却在包裹软骨形成中心的外周间充质中发育。经典研究表明肢体外胚层作为肢体软骨形成的负调节剂。在本文中，我们研究了外胚层对体内禽胚胎肢体软骨形成的抑制影响的分子性质。我们发现，早期肢芽中的外胚层消融导致早期软骨形成标记基因（如 Sox9 和胶原蛋白 II）的增加和异位表达，表明肢体外胚层在软骨形成级联的早期阶段抑制肢体软骨形成。为了研究外胚层抑制影响的分子性质，我们异位表达了 Wnt6，这是目前已知的唯一在禽肢外胚层中表达的 Wnt，并发现 Wnt6 过度表达导致早期软骨形成标记基因 Sox9 和胶原蛋白 II 的表达减少。我们的结果表明，外胚层对肢体软骨形成的抑制作用作用于 Sox9 和 II 型胶原蛋白软骨形成的早期阶段。我们将 Wnt6 确定为体内外胚层软骨形成抑制的候选介质。我们提出了表面外胚层 Wnt 介导的肢体向心模式模型。
Pattern formation of the limb skeleton is regulated by a complex interplay of signaling centers located in the ectodermal sheath and mesenchymal core of the limb anlagen, which results, in the forelimb, in the coordinate array of humerus, radius, ulna, carpals, metacarpals and digits. Much less understood is why skeletal elements form only in the central mesenchyme of the limb, whereas muscle anlagen develop in the peripheral mesenchyme ensheathing the chondrogenic center. Classical studies have suggested a role of the limb ectoderm as a negative regulator of limb chondrogenesis. In this paper, we investigated the molecular nature of the inhibitory influence of the ectoderm on limb chondrogenesis in the avian embryo in vivo. We show that ectoderm ablation in the early limb bud leads to increased and ectopic expression of early chondrogenic marker genes like Sox9 and Collagen II, indicating that the limb ectoderm inhibits limb chondrogenesis at an early stage of the chondrogenic cascade. To investigate the molecular nature of the inhibitory influence of the ectoderm, we ectopically expressed Wnt6, which is presently the only known Wnt expressed throughout the avian limb ectoderm, and found that Wnt6 overexpression leads to reduced expression of the early chondrogenic marker genes Sox9 and Collagen II. Our results suggest that the inhibitory influence of the ectoderm on limb chondrogenesis acts on an early stage of chondrogenesis upsteam of Sox9 and Collagen II. We identify Wnt6 as a candidate mediator of ectodermal chondrogenic inhibition in vivo. We propose a model of Wnt-mediated centripetal patterning of the limb by the surface ectoderm.