Nature. 2016 Jul 28;535(7613):542-6. doi: 10.1038/nature18953. Epub 2016 Jul 20.
The transition from fins to limbs was an important terrestrial adaptation, but how this crucial evolutionary shift arose developmentally is unknown. Current models focus on the distinct roles of the apical ectodermal ridge (AER) and the signaling molecules that it secretes during limb and fin outgrowth. In contrast to the limb AER, the AER of the fin rapidly transitions into the apical fold and in the process shuts off AER-derived signals that stimulate proliferation of the precursors of the appendicular skeleton. The differing fates of the AER during fish and tetrapod development have led to the speculation that fin-fold formation was one of the evolutionary hurdles to the AER-dependent expansion of the fin mesenchyme required to generate the increased appendicular structure evident within limbs. Consequently, a heterochronic shift in the AER-to-apical-fold transition has been postulated to be crucial for limb evolution. The ability to test this model has been hampered by a lack of understanding of the mechanisms controlling apical fold induction. Here we show that invasion by cells of a newly identified somite-derived lineage into the AER in zebrafish regulates apical fold induction. Ablation of these cells inhibits apical fold formation, prolongs AER activity and increases the amount of fin bud mesenchyme, suggesting that these cells could provide the timing mechanism proposed in Thorogood's clock model of the fin-to-limb transition. We further demonstrate that apical-fold inducing cells are progressively lost during gnathostome evolution;the absence of such cells within the tetrapod limb suggests that their loss may have been a necessary prelude to the attainment of limb-like structures in Devonian sarcopterygian fish.
从鳍到肢的转变是一个重要的陆地适应,但这种关键的进化转变是如何在发育中产生的还不得而知。目前的模型主要集中在顶端外胚层嵴(AER)及其在肢和鳍生长过程中分泌的信号分子的独特作用。与肢 AER 不同,鳍的 AER 迅速转变为顶端褶皱,并在此过程中关闭了 AER 衍生的信号,这些信号刺激附肢骨骼前体的增殖。鱼和四足动物发育过程中 AER 的不同命运导致人们推测,鳍褶的形成是 AER 依赖性扩展鳍间充质以产生四肢中明显增加的附肢结构的进化障碍之一。因此,AER 到顶端褶皱转变的异时性转变被认为对肢的进化至关重要。缺乏对控制顶端褶皱诱导机制的理解,限制了对该模型进行测试的能力。在这里,我们表明,新鉴定的体节衍生谱系的细胞侵入斑马鱼的 AER 调节顶端褶皱诱导。这些细胞的消融抑制了顶端褶皱的形成,延长了 AER 的活性并增加了鳍芽间充质的数量,这表明这些细胞可能提供了 Thorogood 鳍到肢转变时钟模型中提出的定时机制。我们进一步证明,在颌类动物进化过程中,顶端褶皱诱导细胞逐渐丢失;在四足动物肢中缺乏这些细胞表明,它们的丢失可能是在泥盆纪肉鳍鱼类中获得类似肢的结构的必要前提。
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