A group 13 homeodomain is neither necessary nor sufficient for posterior prevalence in the mouse limb.
A group 13 homeodomain is neither necessary nor sufficient for posterior prevalence in the mouse limb.
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DOI：
10.1016/j.ydbio.2006.05.027
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发表时间：
2006-09
影响因子：
2.7
通讯作者：
Melissa E. Williams;J. Lehoczky;J. Innis
中科院分区：
文献类型：
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作者：
Melissa E. Williams;J. Lehoczky;J. Innis
后向流行是HOX蛋白的一般特性，描述了更多后向HOX蛋白在共同表达区域对前向同源蛋白功能的主导作用。为了探索这种特性所需的HOX组13蛋白结构域，我们使用小鼠Prx-1启动子在发育过程中驱动HOX构建体在整个肢体芽中的转基因表达。这个系统使我们最终证明了Hox功能在四肢发育中的层次结构。此外，通过将HOXD11或HOXA9同位域替换为HOXD13的同位域，我们发现HOXD13同位域对于后验患病率并不是必需的。这些嵌合蛋白的近端表达出乎意料地导致了与野生型HOXD13介导的后验患病率一致的缺陷。此外，第13组非同源结构域残基似乎赋予了这种特性，因为含有HOXD13同源结构域的HOXA9的近端表达不会导致HOXD13的肢体减少特征。这些数据与基于蛋白质相互作用的后验患病率模型最为一致，并支持将Hox组13蛋白的n端非同质结构域区域作为后验患病率的必要因素进行检查。
Posterior prevalence is the general property attributed to HOX proteins describing the dominant effect of more posterior HOX proteins over the function of anterior orthologs in common areas of expression. To explore the HOX group 13 protein domains required for this property, we used the mouse Prx-1 promoter to drive transgenic expression of Hox constructs throughout the entire limb bud during development. This system allowed us to conclusively demonstrate a hierarchy of Hox function in developing limbs. Furthermore, by substituting the HOXD11 or HOXA9 homeodomain for that of HOXD13, we show that a HOXD13 homeodomain is not necessary for posterior prevalence. Proximal expression of these chimeric proteins unexpectedly caused defects consistent with wild-type HOXD13 mediated posterior prevalence. Moreover, group 13 non-homeodomain residues appear to confer the property as proximal expression of HOXA9 containing the HOXD13 homeodomain did not result in limb reductions characteristic of HOXD13. These data are most compatible with models of posterior prevalence based on protein–protein interactions and support examination of the N-terminal non-homeodomain regions of Hox group 13 proteins as necessary agents for posterior prevalence.