SHH Protein Variance in the Limb Bud Is Constrained by Feedback Regulation and Correlates with Altered Digit Patterning.
SHH Protein Variance in the Limb Bud Is Constrained by Feedback Regulation and Correlates with Altered Digit Patterning.
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DOI：
10.1534/g3.116.033019
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发表时间：
2017-03-10
期刊：
影响因子：
--
通讯作者：
Harfe BD
中科院分区：
文献类型：
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作者：
Zhang R;Lee C;Lawson LY;Svete LJ;McIntyre LM;Harfe BD
mRNA变异在正常发育、群体适应性、适应性和疾病中起着关键作用。虽然基因表达水平的变化可能有利于某些细胞过程，例如细胞对外部刺激的反应能力，但变化可能不利于某些器官的发育。在两侧对称的脊椎动物肢芽中，在特定发育阶段存在的Sonic Hedgehog（SHH）蛋白的量对于确保该结构的适当模式是必不可少的。令我们惊讶的是，我们发现SHH蛋白的变异存在于肢体发育的前10小时。在肢体发育的前10小时后，差异几乎被消除。通过研究突变动物，我们确定了肢芽顶端外胚层嵴（AER）对SHH蛋白的反应能力是在肢形成过程中减少SHH变异所必需的。未能消除SHH蛋白变异的一个后果是多指畸形和指长增加。这些数据表明了一种潜在的新机制，即在进化过程中SHH变异的改变可能驱动了肢体模式和手指长度的变化。
mRNA variance has been proposed to play key roles in normal development, population fitness, adaptability, and disease. While variance in gene expression levels may be beneficial for certain cellular processes, for example in a cell’s ability to respond to external stimuli, variance may be detrimental for the development of some organs. In the bilaterally symmetric vertebrate limb buds, the amount of Sonic Hedgehog (SHH) protein present at specific stages of development is essential to ensure proper patterning of this structure. To our surprise, we found that SHH protein variance is present during the first 10 hr of limb development. The variance is virtually eliminated after the first 10 hr of limb development. By examining mutant animals, we determined that the ability of the limb bud apical ectodermal ridge (AER) to respond to SHH protein was required for reducing SHH variance during limb formation. One consequence of the failure to eliminate variance in SHH protein was the presence of polydactyly and an increase in digit length. These data suggest a potential novel mechanism in which alterations in SHH variance during evolution may have driven changes in limb patterning and digit length.