N-cadherin is not essential for limb mesenchymal chondrogenesis
N-cadherin is not essential for limb mesenchymal chondrogenesis
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DOI：
10.1002/dvdy.20241
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发表时间：
2005-02-01
影响因子：
2.5
通讯作者：
Radice, GL
中科院分区：
文献类型：
--
作者：
Luo, Y;Kostetskii, I;Radice, GL
细胞黏附分子N-钙粘附素参与了许多形态发生过程，包括肢体发育过程中的间质凝聚。为了进一步了解N-钙粘蛋白的功能，我们在小鼠N-钙粘蛋白启动子的调控下，鉴定了一个新的含有LacZ报告基因的N-钙粘蛋白等位基因。报告基因概括了N-钙粘蛋白基因的表达模式，包括在心脏、神经管和体节中的表达。此外，在活跃的细胞凝聚区也观察到强烈的表达，这是软骨分化的先决条件，包括发育中的下颌骨、椎骨和四肢。我们实验室以前的研究表明，表达心脏特异性钙粘素转基因的N-钙粘素缺失胚胎可以形成肢体芽，然而，这些部分挽救的胚胎存活时间不足以观察肢体发育。为了克服胚胎致死性，我们使用了器官培养系统来检查肢体的体外发育。我们证明了N-钙粘附素缺乏的肢体芽能够间充质凝聚和软骨形成，导致骨骼结构。与以前在鸡身上使用N-钙粘素干扰抗体进行的研究不同，我们的小鼠组织器官培养研究表明，N-钙粘附素对肢体间充质软骨形成不是必不可少的。我们推测，另一种细胞黏附分子，可能是钙粘附素-11，负责N-钙粘附素缺乏肢体的软骨形成。(C)2004年Wiley-Liss公司
The cell adhesion molecule N-cadherin is implicated in many morphogenetic processes, including mesenchyme condensation during limb development. To further understand N-cadherin function, we characterized a new N-cadherin allele containing the lacZ reporter gene under the regulation of the mouse N-cadherin promoter. The reporter gene recapitulates the expression pattern of the N-cadherin gene, including expression in heart, neural tube, and somites. In addition, strong expression was observed in areas of active cellular condensation, a prerequisite for chondrogenic differentiation, including the developing mandible, vertebrae, and limbs. Previous studies from our laboratory have shown that limb buds can form in N-cadherin-null embryos expressing a cardiac-specific cadherin transgene, however, these partially rescued embryos do not survive long enough to observe limb development. To overcome the embryonic lethality, we used an organ culture system to examine limb development ex vivo. We demonstrate that N-cadherin-deficient limb buds were capable of mesenchymal condensation and chondrogenesis, resulting in skeletal structures. In contrast to previous studies in chicken using N-cadherin-perturbing antibodies, our organ culture studies with mouse tissue demonstrate that N-cadherin is not essential for limb mesenchymal chondrogenesis. We postulate that another cell adhesion molecule, possibly cadherin-11, is responsible for chondrogenesis in the N-cadherin-deficient limb. (C) 2004 Wiley-Liss, Inc.