Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes
Noncanonical frizzled signaling regulates cell polarity of growth plate chondrocytes
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DOI：
10.1242/dev.023820
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发表时间：
2009-04-01
期刊：
影响因子：
4.6
通讯作者：
Dudley, Andrew T.
中科院分区：
文献类型：
--
作者：
Li, Yuwei;Dudley, Andrew T.
骨骼的生长是由细胞增殖和随后的软骨细胞肥大推动的，软骨细胞排列在盘状细胞柱中，类似于成堆的硬币。然而，指导骨柱形成的分子机制以及骨柱组织对骨形态发生的重要性尚不清楚。在这里，我们展示了鸡的盘状增殖性软骨细胞定位于分裂平面，以产生子代细胞，这些子代细胞最初被横向移位，然后插入柱状。FZD信号的下调改变了长骨的尺寸，并在增殖的软骨细胞组织中产生了细胞自主性的变化，其特征是任意的分裂平面和改变的细胞堆积。这些缺陷是通过非规范效应通路的中断而不是通过规范FZD信号的抑制剂来表现出来的。这些发现表明，非规范的FZD信号对细胞极性和细胞排列的调节在形成独特的形态特征方面发挥了重要作用，这些特征塑造了单个软骨元素。
Bone growth is driven by cell proliferation and the subsequent hypertrophy of chondrocytes arranged in columns of discoid cells that resemble stacks of coins. However, the molecular mechanisms that direct column formation and the importance of columnar organization to bone morphogenesis are not known. Here, we show in chick that discoid proliferative chondrocytes orient the division plane to generate daughter cells that are initially displaced laterally and then intercalate into the column. Downregulation of frizzled (Fzd) signaling alters the dimensions of long bones and produces cell-autonomous changes in proliferative chondrocyte organization characterized by arbitrary division planes and altered cell stacking. These defects are phenocopied by disruption of noncanonical effector pathways but not by inhibitors of canonical Fzd signaling. These findings demonstrate that the regulation of cell polarity and cell arrangement by noncanonical Fzd signaling plays important roles in generating the unique morphological characteristics that shape individual cartilage elements.