Kumar Anoop, Gates Phillip B, Czarkwiani Anna, Brockes Jeremy P
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
Department of Genetics, Evolution and Environment, Division of Biosciences, University College London, London WC1E 6BT, UK.
Nat Commun. 2015 Oct 26;6:8684. doi: 10.1038/ncomms9684.
Limb development in salamanders differs from other tetrapods in that the first digits to form are the two most anterior (preaxial dominance). This has been proposed as a salamander novelty and its mechanistic basis is unknown. Salamanders are the only adult tetrapods able to regenerate the limb, and the contribution of preaxial dominance to limb regeneration is unclear. Here we show that during early outgrowth of the limb bud, a small cohort of cells express the orphan gene Prod1 together with Bmp2, a critical player in digit condensation in amniotes. Disruption of Prod1 with a gene-editing nuclease abrogates these cells, and blocks formation of the radius and ulna, and outgrowth of the anterior digits. Preaxial dominance is a notable feature of limb regeneration in the larval newt, but this changes abruptly after metamorphosis so that the formation of anterior and posterior digits occurs together within the autopodium resembling an amniote-like pattern.
蝾螈的肢体发育与其他四足动物不同，其最先形成的指是最靠前的两个（前轴优势）。这被认为是蝾螈的一个新奇特征，其机制基础尚不清楚。蝾螈是唯一能够再生肢体的成年四足动物，前轴优势对肢体再生的贡献尚不清楚。在这里，我们表明，在肢芽早期生长过程中，一小群细胞同时表达孤儿基因Prod1和Bmp2，Bmp2是羊膜动物指凝聚过程中的关键因子。用基因编辑核酸酶破坏Prod1会消除这些细胞，并阻止桡骨和尺骨的形成以及前指的生长。前轴优势是幼体蝾螈肢体再生的一个显著特征，但在变态后这一特征会突然改变，从而使得前指和后指在足板内一起形成，类似于羊膜动物的模式。
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