Malkmus Jonas, Morabito Angela, Lopez-Delisle Lucille, Avino-Esteban Laura, Mayran Alexandre, Zuniga Aimee, Sharpe James, Zeller Rolf, Sheth Rushikesh
Developmental Genetics, Department of Biomedicine, University of Basel, CH4054 Basel, Switzerland.
School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), CH 1015 Lausanne, Switzerland.
Development. 2025 Jun 1;152(11). doi: 10.1242/dev.204606. Epub 2025 Jun 10.
Self-organization, such as the emergence of a pattern from a homogenous state, is a fascinating property of biological systems. Early limb bud outgrowth and patterning in mice are controlled by a robust and self-regulatory signaling system, and initiation of the periodic digit-interdigit pattern appears to be under the control of a self-regulatory Turing system. Previous studies established the requirement of WNT and BMP signaling for both early limb bud and digit-interdigit morphogenesis, but the molecular changes underlying the transition from early limb bud signaling to the digit-interdigit patterning system remained unknown. Here, we have used small molecule inhibitors to rapidly but transiently block WNT signaling to identify the early transcriptional targets that are altered during disruption and recovery of limb bud and digit development. Together, this study highlights the overarching role of WNT signaling in controlling early limb bud outgrowth and patterning, and the establishment of the periodic digit-interdigit pattern. Finally, the transient WNT signaling disruption approach reveals the plasticity and robustness of these self-organizing limb bud- and digit-patterning systems.
自组织，例如从均匀状态中出现一种模式，是生物系统的一个迷人特性。小鼠早期肢芽的生长和模式形成由一个强大的自我调节信号系统控制，而周期性指-指间隙模式的起始似乎受一个自我调节的图灵系统控制。先前的研究确定了WNT和BMP信号对于早期肢芽和指-指间隙形态发生的必要性，但从早期肢芽信号传导过渡到指-指间隙模式形成系统背后的分子变化仍然未知。在这里，我们使用小分子抑制剂快速但短暂地阻断WNT信号，以识别在肢芽和指发育的破坏和恢复过程中发生改变的早期转录靶点。总之，这项研究突出了WNT信号在控制早期肢芽生长和模式形成以及周期性指-指间隙模式建立中的首要作用。最后，短暂的WNT信号破坏方法揭示了这些自组织的肢芽和指模式形成系统的可塑性和稳健性。
