Molecular anatomy of the developing limb in the coquí frog, Eleutherodactylus coqui.
Molecular anatomy of the developing limb in the coquí frog, Eleutherodactylus coqui.
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DOI：
10.1111/j.1525-142x.2011.00500.x
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发表时间：
2011-09
影响因子：
2.9
通讯作者：
Tabin CJ
中科院分区：
文献类型：
--
作者：
Gross JB;Kerney R;Hanken J;Tabin CJ
脊椎动物的肢体在系统发育上不同的群体中表现出显著的相似性。为了进一步了解这种形态相似性是如何在不同的发育背景下保持的，我们探索了波多黎各coquí青蛙（Eleutherodactylus coqui）缩小胚胎的分子解剖学。这种动物展示了直接发育，这是一种以从卵到成虫的快速发展为标志的生活史策略，没有自由生活的水生幼虫。尽管如此，coquí展示了一个基础的无尾猿肢体结构，前肢有四个脚趾，后肢有五个脚趾。我们调查了coquí肢体芽发育在多大程度上符合羊膜研究衍生的肢体发育模型。为此，我们在肢体发育的三个主要阶段表征了13个关键模式基因的动态表达模式。正如预期的那样，与羊膜动物相比，大多数基因表现出的表达模式基本不变。例如，我们在顶端外胚层脊（AER）中发现了一个ecfgf8表达域。这种表达模式定义了一个假定的功能性AER信号域，尽管在coquí胚胎中没有形态嵴。然而，两个基因EcMeis2和EcAlx4表现出表达域的改变，这意味着coquí青蛙和羊膜模型系统之间基因功能的潜在转变。出乎意料的是，在我们分析的三个阶段中，包括EcFgf4、EcWnt3a、EcWnt7a和EcGremlin在内的几个在其他系统中被认为对肢体模式至关重要的基因在肢体中没有明显的表达模式。基于敲除和表达分析，在肢体模式形成过程中缺乏EcFgf4和EcWnt3a的表达可能并不令人惊讶，因为这两个基因对小鼠的正常肢体发育都不重要。相比之下，EcWnt7a和EcGremlin的缺失令人惊讶，因为到目前为止，这些分子的表达似乎在所有其他模型系统中都是绝对必要的。因此，虽然这一分析证实了一组核心的古代肢体模式分子的存在，这些分子可能在高度多样化的脊椎动物形态中介导相同的功能，但它也揭示了在进化时间中遗传控制保守形态模式的显着进化灵活性。
The vertebrate limb demonstrates remarkable similarity in basic organization across phylogenetically disparate groups. To gain further insight into how this morphological similarity is maintained in different developmental contexts, we explored the molecular anatomy of size-reduced embryos of the Puerto Rican coquí frog, Eleutherodactylus coqui. This animal demonstrates direct development, a life history strategy marked by rapid progression from egg to adult and absence of a free-living, aquatic larva. Nonetheless, coquí exhibits a basal anuran limb structure, with four toes on the forelimb and five toes on the hind limb. We investigated the extent to which coquí limb bud development conforms to the model of limb development derived from amniote studies. Towards this end, we characterized dynamic patterns of expression for 13 critical patterning genes across three principle stages of limb development. As expected, most genes demonstrate expression patterns that are essentially unchanged compared to amniote species. For example, we identified an EcFgf8-expression domain within the apical ectodermal ridge (AER). This expression pattern defines a putatively functional AER signalling domain, despite the absence of a morphological ridge in coquí embryos. However, two genes, EcMeis2 and EcAlx4, demonstrate altered domains of expression, which imply a potential shift in gene function between coquí frogs and amniote model systems. Unexpectedly, several genes thought to be critical for limb patterning in other systems, including EcFgf4, EcWnt3a, EcWnt7a and EcGremlin, demonstrated no evident expression pattern in the limb at the three stages we analyzed. The absence of EcFgf4 and EcWnt3a expression during limb patterning is perhaps not surprising, given that neither gene is critical for proper limb development in the mouse, based on knock-out and expression analyses. In contrast, absence of EcWnt7a and EcGremlin is surprising, given that expression of these molecules appears to be absolutely essential in all other model systems so far examined. Thus, while this analysis substantiates the existence of a core set of ancient limb-patterning molecules, which likely mediate identical functions across highly diverse vertebrate forms, it also reveals remarkable evolutionary flexibility in the genetic control of a conserved morphological pattern across evolutionary time.