A hierarchy of Runx transcription factors modulate the onset of chondrogenesis in craniofacial endochondral bones in zebrafish
A hierarchy of Runx transcription factors modulate the onset of chondrogenesis in craniofacial endochondral bones in zebrafish
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DOI：
10.1002/dvdy.20957
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发表时间：
2006-11-01
影响因子：
2.5
通讯作者：
Crosier, Kathryn
中科院分区：
文献类型：
--
作者：
Flores, Maria Vega;Lam, Enid Yi Ni;Crosier, Kathryn
Runx（runt 相关）转录因子家族是早期胚胎发育以及包括血液、神经元和骨骼在内的组织分化中细胞命运决定的重要调节因子。在哺乳动物的骨骼发育过程中，虽然只有 Runx2 对于成骨细胞分化至关重要，但所有家族成员似乎都参与软骨形成。 Runx2 和 Runx3 控制软骨细胞成熟。 Runx1 和 Runx2 均在间充质凝结的早期表达，但它们如何促进软骨细胞分化的初始阶段尚不清楚。在这里，我们展示了 Runx 转录调控的层次结构促进了斑马鱼头部骨骼中软骨细胞从前软骨间质分化的早期程序。我们之前已经对所有 Runx 基因的斑马鱼直向同源物进行了表征。斑马鱼 runx2 重复，但 runx1 或 runx3 不重复。在此介绍的工作中，我们确定了颅面部区域 runx 基因的早期表达模式。最早检测到的表达是咽内胚层中的runx3，然后是间充质凝结中的runx2a和b，最后是上皮中的runx1。使用反义吗啉敲低分析，我们检查了它们在早期软骨形成中各自的活性。 runx2b（但不是runx2a）和runx3的耗尽严重损害了颅面软骨的形成。由于 Runx2b 表达在 Runx3 变形体中被消除，因此我们认为内胚层 Runx3 具有影响内胚层信号传导活动以促进软骨细胞分化的作用。我们还表明，与小鼠研究的数据相比，斑马鱼 Runx1 在导致软骨内骨形成的软骨形成的初始步骤中不是必需的。
The Runx (runt-related) family of transcription factors are important regulators of cell fate decisions in early embryonic development, and in differentiation of tissues including blood, neurons, and bone. During skeletal development in mammals, while only Runx2 is essential for osteoblast differentiation, all family members seem to be involved in chondrogenesis. Runx2 and Runx3 control chondrocyte maturation. Both Runx1 and Runx2 are expressed early in mesenchymal condensations, but how they contribute to the initial stages of chondrocyte differentiation is unclear. Here we show that a hierarchy of Runx transcriptional regulation promotes the early program of chondrocyte differentiation from pre-cartilage mesenchyme in the zebrafish head skeleton. We have previously characterized the zebrafish orthologs for all Runx genes. Zebrafish runx2 is duplicated, but not runx1 or runx3. In the work presented here, we determined the early expression pattern of the runx genes in the craniofacial region. The earliest expression detected was that of runx3 in the pharyngeal endoderm, then runx2a and b in mesenchymal condensations, and later runx1 in the epithelium. Using antisense morpholino knockdown analysis, we examined their respective activities in early chondrogenesis. Depletion of runx2b (but not runx2a) and runx3 severely compromised craniofacial cartilage formation. Because runx2b expression was abolished in Runx3 morphants, we propose that endodermal Runx3 has a role in influencing signaling activities from the endoderm to promote chondrocyte differentiation. We also show that, in contrast to data from mouse studies, zebrafish Runx1 is not required in the initial steps of chondrogenesis leading to endochondral bone formation.