Runx2 is essential for larval hyobranchial cartilage formation in Xenopus laevis

Runx2 is essential for larval hyobranchial cartilage formation in Xenopus laevis
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DOI:
10.1002/dvdy.21175
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发表时间:
2007-06-01
影响因子:
2.5
通讯作者:
Hanken, James
Hanken, James
中科院分区:
生物学3区
文献类型:
--
作者:
Kerney, Ryan;Gross, Joshua B.;Hanken, James

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脊椎动物转录因子蛋白Runx 2被认为是骨形成的“主调节器”,这是由于在小鼠纯合敲除中骨骨架的急剧损失。然而,Runx2 mRNA也在小鼠和鸡的肥大前软骨骨骼中表达,其发育功能在很大程度上是未知的。Runx2调控存在于小鼠中的几个层次,其中任何一个都可以解释其在骨骼发生早期阶段的生物学活性。与小鼠和鸡不同,斑马鱼在早期软骨分化中需要Runx2功能。本研究揭示了Runx2在软骨分化中的早期功能作用在斑马鱼和非洲爪蟾之间是共享的。吗啉寡核苷酸注射和神经嵴移植的组合表明,Runx2参与分化的软骨下鳃骨架的青蛙,非洲爪蟾。此外,原位杂交显示软骨颅骨的间充质前体中有runx2 mRNA表达,这揭示了迄今为止所描述的这些软骨的最早的预图案化。runx2的早期分布解决了幼虫的喙上板的同源性,这是无尾目头骨发育的最古老的争议之一。总之,这些数据揭示了Runx2蛋白功能在脊椎动物进化过程中向其在软骨肥大和骨分化中的独特作用的转变。
The vertebrate transcription factor protein Runx2 is regarded as a "master regulator" of bone formation due to the dramatic loss of the osseous skeleton in the mouse homozygous knockout. However, Runx2 mRNA also is expressed in the pre-hypertrophic cartilaginous skeleton of the mouse and chicken, where its developmental function is largely unknown. Several tiers of Runx2 regulation exist in the mouse, any of which may account for its seeming biological inactivity during early stages of skeletogenesis. Unlike mouse and chicken, zebrafish require Runx2 function in early cartilage differentiation. The present study reveals that the earlier functional role of Runx2 in cartilage differentiation is shared between zebrafish and Xenopus. A combination of morpholino oligonucleotide injections and neural crest transplants indicate that Runx2 is involved in differentiation of the cartilaginous hyobranchial skeleton in the frog, Xenopus laevis. Additionally, in situ hybridizations show runx2 mRNA expression in mesenchymal precursors of the cartilaginous skull, which reveals the earliest pre-patterning of these cartilages described to date. The early distribution of runx2 resolves the homology of the larval suprarostral plate, which is one of the oldest controversies of anuran skull development. Together these data reveal a shift in Runx2 protein function during vertebrate evolution towards its exclusive roles in cartilage hypertrophy and bone differentiation within the amniote lineage.