Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice
Misexpression of Sox9 in mouse limb bud mesenchyme induces polydactyly and rescues hypodactyly mice
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DOI：
10.1016/j.matbio.2006.12.002
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发表时间：
2007-05-01
期刊：
影响因子：
6.9
通讯作者：
de Crombrugghe, Benoit
中科院分区：
文献类型：
--
作者：
Akiyama, Haruhiko;Stadler, H. Scott;de Crombrugghe, Benoit
我们先前的研究已经证明了转录因子Sox 9在间充质细胞向软骨细胞谱系的承诺和在肢芽发育过程中的明显软骨形成中的重要作用。然而，它仍然是未知的，如果Sox 9诱导间充质异位体内软骨形成的主调节器的软骨形成。在这项研究中，我们首先产生突变小鼠，其中Sox 9在肢芽间充质中错误表达。突变小鼠胚胎表现出多趾肢芽与异位表达的Sox 5和Sox 6，虽然标记的不同轴的肢芽发育表现出正常的表达模式。Sox 9的错误表达刺激了肢芽间充质细胞的增殖，表明Sox 9在招募间充质细胞进行间充质凝聚中具有作用。其次，尽管事实上，错误表达的Sonic hedgehog（Shh）诱导多趾畸形在一些突变小鼠和Shh无效突变体有严重缺陷的软骨元素在肢芽，错误表达的Sox 9没有恢复肢芽表型在Shh无效突变体。相反，有没有表达的Sox 9在数字I的Hoxa 13 Hd突变胚胎，和Sox 9部分拯救缺趾Hoxa 13 Hd突变胚胎。这些结果提供的证据表明，Sox 9诱导异位软骨间充质细胞，并强烈表明，其表达可能是由Hox基因在肢芽发育。(C)2006年Elsevier B. V./国际矩阵生物学学会。All rights reserved.
Our previous studies have demonstrated the essential roles of the transcription factor Sox9 in the commitment of mesenchymal cells to a chondrogenic cell lineage and in overt chondrogenesis during limb bud development. However, it remains unknown if Sox9 induces chondrogenesis in mesenchyme ectopically in vivo as a master regulator of chondrogenesis. In this study, we first generated mutant mice in which Sox9 was misexpressed in the limb bud mesenchyme. The mutant mouse embryos exhibited polydactyly in limb buds in association with ectopic expression of Sox5 and Sox6 although markers for the different axes of limb bud development showed a normal pattern of expression. Misexpression of Sox9 stimulated cell proliferation in limb bud mesenchyme, suggesting that Sox9 has a role in recruiting mesenchymal cells to mesenchymal condensation. Second, despite the facts that misexpression of Sonic hedgehog (Shh) induces polydactyly in a number of mutant mice and Shh-null mutants have severely defective cartilage elements in limb buds, misexpression of Sox9 did not restore limb bud phenotypes in Shh-null mutants. Rather, there was no expression of Sox9 in digit I of Hoxa13Hd mutant embryos, and Sox9 partially rescued hypodactyly in Hoxa13Hd mutant embryos. These results provide evidence that Sox9 induces ectopic chondrogenesis in mesenchymal cells and strongly suggest that its expression may be regulated by Hox genes during limb bud development. (C) 2006 Elsevier B.V./International Society of Matrix Biology. All rights reserved.