Metscher Brian D, Takahashi Kazuhiko, Crow Karen, Amemiya Chris, Nonaka Daisuke F, Wagner Günter P
Department of Biology, University of Southern Indiana, Evansville, IN 47712, USA.
Evol Dev. 2005 May-Jun;7(3):186-95. doi: 10.1111/j.1525-142X.2005.05021.x.
Summary Paleontological and anatomical evidence suggests that the autopodium (hand or foot) is a novel feature that distinguishes limbs from fins, while the upper and lower limb (stylopod and zeugopod) are homologous to parts of the sarcopterygian paired fins. In tetrapod limb development Hoxa-11 plays a key role in differentiating the lower limb and Hoxa-13 plays a key role in differentiating the autopodium. It is thus important to determine the ancestral functions of these genes in order to understand the developmental genetic changes that led to the origin of the tetrapod autopodium. In particular it is important to understand which features of gene expression are derived in tetrapods and which are ancestral in bony fishes. To address these questions we cloned and sequenced the Hoxa-11 and Hoxa-13 genes from the North American paddlefish, Polyodon spathula, a basal ray-finned fish that has a pectoral fin morphology resembling that of primitive bony fishes ancestral to the tetrapod lineage. Sequence analysis of these genes shows that they are not orthologous to the duplicated zebrafish and fugu genes. This implies that the paddlefish has not duplicated its HoxA cluster, unlike zebrafish and fugu. The expression of Hoxa-11 and Hoxa-13 in the pectoral fins shows two main phases: an early phase in which Hoxa-11 is expressed proximally and Hoxa-13 is expressed distally, and a later phase in which Hoxa-11 and Hoxa-13 broadly overlap in the distal mesenchyme of the fin bud but are absent in the proximal fin bud. Hence the distal polarity of Hoxa-13 expression seen in tetrapods is likely to be an ancestral feature of paired appendage development. The main difference in HoxA gene expression between fin and limb development is that in tetrapods (with the exception of newts) Hoxa-11 expression is suppressed by Hoxa-13 in the distal limb bud mesenchyme. There is, however, a short period of limb bud development where Hoxa-11 and Hoxa-13 overlap similarly to the late expression seen in zebrafish and paddlefish. We conclude that the early expression pattern in tetrapods is similar to that seen in late fin development and that the local exclusion by Hoxa-13 of Hoxa-11 from the distal limb bud is a derived feature of limb developmental regulation.
古生物学和解剖学证据表明，手足（手或脚）是将肢体与鳍区分开来的一个新特征，而上肢和下肢（肢柱骨和连接骨）与肉鳍鱼类的成对鳍的部分同源。在四足动物肢体发育中，Hoxa - 11在下肢分化中起关键作用，Hoxa - 13在手足分化中起关键作用。因此，确定这些基因的原始功能对于理解导致四足动物手足起源的发育遗传变化很重要。特别重要的是要了解哪些基因表达特征是四足动物特有的，哪些是硬骨鱼类所固有的。为了解决这些问题，我们从北美匙吻鲟（Polyodon spathula）中克隆并测序了Hoxa - 11和Hoxa - 13基因，匙吻鲟是一种基干辐鳍鱼，其胸鳍形态类似于四足动物谱系祖先的原始硬骨鱼类。对这些基因的序列分析表明，它们与斑马鱼和河豚的重复基因不是直系同源的。这意味着与斑马鱼和河豚不同，匙吻鲟没有复制其HoxA基因簇。Hoxa - 11和Hoxa - 13在胸鳍中的表达显示出两个主要阶段：早期阶段，Hoxa - 11在近端表达，Hoxa - 13在远端表达；后期阶段，Hoxa - 11和Hoxa - 13在鳍芽的远端间充质中广泛重叠，但在近端鳍芽中不存在。因此，在四足动物中看到的Hoxa - 13表达的远端极性可能是成对附肢发育的一个原始特征。鳍和肢体发育之间HoxA基因表达的主要差异在于，在四足动物（蝾螈除外）中，Hoxa - 11在远端肢体芽间充质中的表达被Hoxa - 13抑制。然而，在肢体芽发育的短时期内，Hoxa - 11和Hoxa - 13的重叠类似于在斑马鱼和匙吻鲟中看到的后期表达。我们得出结论，四足动物的早期表达模式与鳍发育后期的模式相似，并且Hoxa - 13将Hoxa - 11从远端肢体芽中局部排除是肢体发育调控的一个衍生特征。
