Urodele amphibians such as the axolotl regenerate complete limbs as adults, and understanding how the "blueprint", or pattern, of the regenerate is established and manipulated are areas of intense interest. Nutrient signaling plays an important role in pattern formation during regeneration. Retinoic acid signaling is the most characterized pathway during this process. Exogenous retinoic acid (RA) reprograms the pattern information in regenerating cells to a more posterior, ventral, and proximal identity. Vitamin D signaling shares several molecular similarities with RA and has been shown to alter pattern formation during zebrafish pectoral fin regeneration. To determine if exogenous Vitamin D signaling is capable of reprograming pattern in the axolotl limb blastema, we treated regenerating limbs with a potent Vitamin D agonist. Under the studied conditions, exogenous Vitamin D did not act in a manner similar to RA and failed to proximalize the pattern of the resulting regenerates. The Vitamin D treatment did result in several skeletal defects during regeneration, including carpal fusions along the A/P axis; failure to integrate the newly regenerated tissue with the existing tissue, formation of ectopic nodules of cartilage at the site of amputation, and altered bone morphology in uninjured skeletal tissue.

中文翻译：

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外源维生素 D 信号改变蝾螈肢体再生过程中的骨骼模式、分化和组织整合

像蝾螈这样的有尾目两栖动物成年后会再生出完整的四肢，了解再生的“蓝图”或模式是如何建立和操纵的是人们非常感兴趣的领域。营养信号在再生过程中的模式形成中起着重要作用。视黄酸信号传导是该过程中最具特征的途径。外源性视黄酸（RA）将再生细胞的模式信息重新编程为更靠后、腹侧和近端的特征。维生素 D 信号传导与 RA 有一些分子相似性，并且已被证明可以改变斑马鱼胸鳍再生过程中的模式形成。为了确定外源性维生素 D 信号传导是否能够重新编程蝾螈肢体胚基中的模式，我们用强效维生素 D 激动剂治疗再生肢体。在研究条件下，外源性维生素 D 的作用方式与 RA 不同，并且未能使所得再生模式接近。维生素 D 治疗确实导致再生过程中出现多种骨骼缺陷，包括沿 A/P 轴的腕骨融合；新再生的组织未能与现有组织整合，在截肢部位形成异位软骨结节，以及未受伤骨骼组织中骨形态的改变。