Wnt Signaling Coordinates the Expression of Limb Patterning Genes During Axolotl Forelimb Development and Regeneration.
Wnt Signaling Coordinates the Expression of Limb Patterning Genes During Axolotl Forelimb Development and Regeneration.
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DOI：
10.3389/fcell.2022.814250
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发表时间：
2022
影响因子：
5.5
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截肢后，蝾螈可以再生肢体，但肢体再生在多大程度上再现肢体发育尚不清楚。回答这个问题的一个限制是我们缺乏对蝾螈肢体发育的了解。在这里，我们通过研究蝾螈肢体发育和再生过程中肢体模式重要基因的表达模式来解决这个问题。我们关注Wnt信号通路，因为它在四足动物肢体发育过程中调节多种功能，包括肢体芽的形成、生长、模式和骨骼分化。我们使用荧光原位杂交技术来显示Wnt配体、Wnt受体和肢体模式基因在肢体发育和再生中的表达。在肢体发育早期治疗时，抑制Wnt配体分泌永久性地阻断肢体芽的生长。在肢体生长过程中抑制Wnt信号会降低关键信号基因的表达，包括Fgf10、Fgf8和Shh，从而导致肢体生长减少。基因表达模式在发育和再生肢体之间是相似的。再生过程中Wnt信号的抑制同样影响了模式基因的表达。总的来说，我们的研究结果表明肢体发育和再生类似地利用Wnt信号。这也为蝾螈肢体发育和再生过程中Wnt信号通路与其他信号通路的相互作用提供了新的见解。
After amputation, axolotl salamanders can regenerate their limbs, but the degree to which limb regeneration recapitulates limb development remains unclear. One limitation in answering this question is our lack of knowledge about salamander limb development. Here, we address this question by studying expression patterns of genes important for limb patterning during axolotl salamander limb development and regeneration. We focus on the Wnt signaling pathway because it regulates multiple functions during tetrapod limb development, including limb bud initiation, outgrowth, patterning, and skeletal differentiation. We use fluorescence in situ hybridization to show the expression of Wnt ligands, Wnt receptors, and limb patterning genes in developing and regenerating limbs. Inhibition of Wnt ligand secretion permanently blocks limb bud outgrowth when treated early in limb development. Inhibiting Wnt signaling during limb outgrowth decreases the expression of critical signaling genes, including Fgf10, Fgf8, and Shh, leading to the reduced outgrowth of the limb. Patterns of gene expression are similar between developing and regenerating limbs. Inhibition of Wnt signaling during regeneration impacted patterning gene expression similarly. Overall, our findings suggest that limb development and regeneration utilize Wnt signaling similarly. It also provides new insights into the interaction of Wnt signaling with other signaling pathways during salamander limb development and regeneration.