Raymond Michael J, Cherubino Matthew A, Vieira Warren A, Manon Sheyla, McCusker Catherine D
College of Science and Mathematics, Department of Biology, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA, 02125, USA.
Commun Biol. 2025 Apr 24;8(1):659. doi: 10.1038/s42003-025-08084-x.
Limb regeneration in the Mexican axolotl relies on the dedifferentiation of mature limb cells into blastema cells, which gain the ability to respond to patterning signals that guide tissue regeneration. While limb nerves are essential to make the blastema cells competent to pattern, the mechanisms remain unclear due to the complex and overlapping signals in amputated limbs. To overcome this challenge, we developed the Competency Accessory Limb Model (CALM), a simplified limb regeneration assay to study the induction and maintenance of patterning competency. Using CALM, here we show specific temporal windows during which cells acquire competency and associate this state with distinct H3K27me3 chromatin signatures. Furthermore, a combination of FGF and BMP signaling is sufficient to induce patterning competency in limb wound cells, and the ErBB signaling pathway is a downstream epigenetic target of these signals. These findings offer new insights into the molecular regulation of regenerative patterning.
墨西哥钝口螈的肢体再生依赖于成熟肢体细胞去分化为芽基细胞，这些芽基细胞获得了对引导组织再生的模式信号作出反应的能力。虽然肢体神经对于使芽基细胞具备模式形成能力至关重要，但由于截肢肢体中信号复杂且相互重叠，其机制仍不清楚。为了克服这一挑战，我们开发了能力辅助肢体模型（CALM），这是一种简化的肢体再生检测方法，用于研究模式形成能力的诱导和维持。利用CALM，我们在此展示了细胞获得能力的特定时间窗口，并将这种状态与不同的H3K27me3染色质特征联系起来。此外，FGF和BMP信号的组合足以诱导肢体伤口细胞的模式形成能力，并且ErBB信号通路是这些信号的下游表观遗传靶点。这些发现为再生模式的分子调控提供了新的见解。
