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首页> 外文期刊>Molecular and Cellular Biology >Identification and Analysis of a Conserved Tcfap2a Intronic Enhancer Element Required for Expression in Facial and Limb Bud Mesenchyme
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Identification and Analysis of a Conserved Tcfap2a Intronic Enhancer Element Required for Expression in Facial and Limb Bud Mesenchyme

机译：在面部和下肢芽间充质中表达所需的保守的Tcfap2a内含子增强子元件的鉴定和分析

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摘要

Tcfap2a, the gene encoding the mouse AP-2α transcription factor, is required for normal development of multiple structures during embryogenesis, including the face and limbs. Using comparative sequence analysis and transgenic-mouse experiments we have identified an intronic enhancer within this gene that directs expression to the face and limb mesenchyme. There are two conserved sequence blocks within this intron, and the larger of these directs tissue-specific activity and is found in all vertebrate Tcfap2a genes analyzed. To assess the role of the enhancer in regulating endogenous mouse Tcfap2a expression, we have deleted this cis-regulatory sequence from the genome. Loss of this element severely impairs Tcfap2a expression in the limb bud mesenchyme but generates only a modest reduction in the facial mesenchyme. The reduction in Tcfap2a transcription is accompanied by altered patterning of the forelimb, resulting in postaxial polydactyly. These results indicate that the major role for this enhancer resides within the limb bud, and it serves to maintain a level of Tcfap2a expression that limits the size of the hand plate and the associated number of digit primordia. The potential role of this cis-acting sequence in modeling the size and shape of the face and limbs during evolution is discussed.
机译：编码小鼠AP-2α转录因子的基因 Tcfap2a 是胚胎发生期间包括面部和四肢在内的多种结构正常发育所必需的。通过比较序列分析和转基因小鼠实验，我们已经鉴定出该基因内的内含子增强子，该增强子将表达引导至面部和四肢间充质。该内含子内有两个保守的序列块，其中较大的一个指导组织特异的活性，并且在所有分析过的脊椎动物 Tcfap2a 基因中都发现了。为了评估增强子在调节内源性小鼠 Tcfap2a 表达中的作用，我们从基因组中删除了该 cis 调控序列。该元素的丧失严重削弱了肢芽间充质细胞中的 Tcfap2a 表达，但仅使面部间质细胞适度减少。 Tcfap2a 转录的减少伴随着前肢图案的改变，从而导致后轴多指畸形。这些结果表明，该增强剂的主要作用在于肢芽内，并可以维持 Tcfap2a 表达水平，从而限制了手板的大小和相关的手指原基数量。讨论了该顺式作用序列在进化过程中面部和四肢的大小和形状建模中的潜在作用。

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