Hyaluronan in limb morphogenesis
Hyaluronan in limb morphogenesis
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DOI：
10.1016/j.ydbio.2007.02.023
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发表时间：
2007-05-15
影响因子：
2.7
通讯作者：
Kosher, Robert A.
中科院分区：
文献类型：
--
作者：
Li, Yingcui;Toole, Bryan P.;Kosher, Robert A.
透明质酸（HA）是一种大的糖胺聚糖，其不仅是细胞外基质的结构组分，而且与细胞表面受体相互作用以促进细胞增殖、迁移和细胞内信号传导。HA是正在发育的肢芽的远端亚顶端间充质细胞的细胞外基质的主要组分，其响应于顶端外胚层嵴（AER）而经历增殖、定向迁移和图案化，并且具有参与这些过程的功能潜力。在这里，我们表明，HA合酶Has 2是丰富的表达的远端subridge中胚层细胞的鸡肢芽，也由AER本身。Has 2的表达和HA的产生下调的近端中央核心的肢芽在形成的骨骼元素的precarcinoma冷凝，这表明HA的下调可能是必要的细胞的紧密并列和由此产生的细胞-细胞相互作用，在冷凝过程中触发软骨分化。在体内，Has 2在鸡的中胚层中的过表达导致形成缺少一个或多个骨骼元件的缩短和严重畸形的肢体。在过度表达Has 2的肢体中确实形成的骨骼元件长度减少，表现出异常形态，并且位置不适当。我们还表明，持续的HA生产在微团培养的肢体间充质细胞抑制形成前软骨冷凝和随后的软骨形成，表明HA的下调确实是必要的前软骨冷凝，触发软骨分化的形成。总之，这些结果表明，HA参与了lirnb形态发生的各个方面。(c)2007爱思唯尔公司All rights reserved.
Hyaluronan (HA) is a large glycosaminoglycan that is not only a structural component of extracellular matrices, but also interacts with cell surface receptors to promote cell proliferation, migration, and intracellular signaling. HA is a major component of the extracellular matrix of the distal subapical mesenchymal cells of the developing limb bud that are undergoing proliferation, directed migration, and patterning in response to the apical ectodermal ridge (AER), and has the functional potential to be involved in these processes. Here we show that the HA synthase Has2 is abundantly expressed by the distal subridge mesodermal cells of the chick limb bud and also by the AER itself. Has2 expression and HA production are downregulated in the proximal central core of the limb bud during the formation of the precartilage condensations of the skeletal elements, suggesting that downregulation of HA may be necessary for the close juxtaposition of cells and the resulting cell-cell interactions that trigger cartilage differentiation during condensation. Overexpression of Has2 in the mesoderm of the chick lirnb bud in vivo results in the formation of shortened and severely malformed limbs that lack one or more skeletal elements. Skeletal elements that do form in limbs overexpressing Has2 are reduced in length, exhibit abnormal morphology, and are positioned inappropriately. We also demonstrate that sustained HA production in micromass cultures of limb mesenchymal cells inhibits formation of precartilage condensations and subsequent chondrogenesis, indicating that downregulation of HA is indeed necessary for formation of the precartilage condensations that trigger cartilage differentiation. Taken together these results suggest involvement of HA in various aspects of lirnb morphogenesis. (c) 2007 Elsevier Inc. All rights reserved.