Arce Hernán, Ceccarelli Alberto Sebastián, Córdoba Rodrigo Carlos, Oliveira Ana Catarina Rodrigues, Yun Maximina Hee, Chara Osvaldo
Instituto de Tecnología, Universidad Argentina de la Empresa, Buenos Aires, Argentina.
School of Biosciences, University of Nottingham, Sutton Bonington Campus, Nottingham, LE12 5RD, UK.
Sci Rep. 2025 Jul 24;15(1):26839. doi: 10.1038/s41598-025-10527-8.
The axolotl (Ambystoma mexicanum) possesses a remarkable ability to regenerate tissues. Following limb amputation, a blastema of progenitor cells forms, expands, and reconstructs all distal structures, implying that mature cells near the wound retain positional memory along the proximal-distal (PD) axis. Key regulators of positional identity, such as Prod1 and Tig1, promote proximalisation-a shift toward a more proximal identity-when overexpressed, but the mechanisms governing this process remain unclear. In this study, we tracked changes in cellular density along the PD axis of regenerating axolotl limbs after transfecting distal blastemas with Tig1 and Prod1, mapping the spatiotemporal distribution of transfected cells and their progeny throughout regeneration. Using a continuous mathematical modelling approach, we predict a proximalisation velocity induced by factors eliciting proximal identity as Prod1 and Tig1, which is consistent with a proximalisation force driven by a positional potential. Our findings provide a foundational framework for understanding how cells acquire positional identity to guide limb regeneration in axolotls.
美西钝口螈（Ambystoma mexicanum）具有非凡的组织再生能力。肢体截肢后，祖细胞形成芽基，芽基生长并重建所有远端结构，这意味着伤口附近的成熟细胞沿近端 - 远端（PD）轴保留位置记忆。位置身份的关键调节因子，如Prod1和Tig1，在过表达时会促进近端化——向更接近近端身份的转变——但控制这一过程的机制仍不清楚。在本研究中，我们在用Tig1和Prod1转染远端芽基后，追踪了再生美西钝口螈肢体PD轴上细胞密度的变化，绘制了转染细胞及其后代在整个再生过程中的时空分布。使用连续数学建模方法，我们预测了由引发近端身份的因子（如Prod1和Tig1）诱导的近端化速度，这与由位置电位驱动的近端化力一致。我们的研究结果为理解细胞如何获得位置身份以指导美西钝口螈肢体再生提供了一个基础框架。
