School of Biosciences, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.
Chester Medical School, Chester, CH2 1BR, UK.
Nat Commun. 2023 Sep 20;14(1):5841. doi: 10.1038/s41467-023-41457-6.
Complex signalling between the apical ectodermal ridge (AER - a thickening of the distal epithelium) and the mesoderm controls limb patterning along the proximo-distal axis (humerus to digits). However, the essential in vivo requirement for AER-Fgf signalling makes it difficult to understand the exact roles that it fulfils. To overcome this barrier, we developed an amenable ex vivo chick wing tissue explant system that faithfully replicates in vivo parameters. Using inhibition experiments and RNA-sequencing, we identify a transient role for Fgfs in triggering the distal patterning phase. Fgfs are then dispensable for the maintenance of an intrinsic mesodermal transcriptome, which controls proliferation/differentiation timing and the duration of patterning. We also uncover additional roles for Fgf signalling in maintaining AER-related gene expression and in suppressing myogenesis. We describe a simple logic for limb patterning duration, which is potentially applicable to other systems, including the main body axis.
顶外胚层嵴（AER-远端上皮增厚）和中胚层之间的复杂信号传导控制着沿近-远轴（肱骨到手指）的肢体模式形成。然而，AER-Fgf 信号传导的基本体内要求使得很难理解它所起的具体作用。为了克服这一障碍，我们开发了一种适合的离体鸡翅膀组织外植体系统，该系统忠实地复制了体内参数。通过抑制实验和 RNA 测序，我们确定 Fgfs 在触发远端模式形成阶段中具有短暂的作用。然后，Fgfs 对于维持内在中胚层转录组是可有可无的，该转录组控制增殖/分化时间和模式形成的持续时间。我们还发现 Fgf 信号传导在维持与 AER 相关的基因表达和抑制成肌发生方面的其他作用。我们描述了一个简单的肢体模式形成持续时间的逻辑，这可能适用于其他系统，包括主体轴。
