Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction–diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction–diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern’s condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) β signalling, which serves to drive chemotactic mesenchymal patterning when reaction–diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis.

有两种理论解决了发育过程中重复模式的起源，例如毛囊，四肢手指和肠绒毛。图灵反应扩散系统认为，相互作用的静态细胞产生的可扩散信号首先定义了一种预模式，然后诱导细胞重排以产生解剖结构。第二种理论是间充质自我组织的理论，提出移动细胞可以直接形成细胞聚集体的周期性模式，而无需参考任何预模式。早期毛囊发育的特征是表皮中基因表达改变的周期性排列的快速出现和邻近的真皮间充质细胞的显着聚集。我们评估毛囊模式中反应扩散与间充质自组织过程之间的关系和相互作用，确定成纤维细胞生长因子（FGF），无翅相关整合位点（WNT）和骨形态发生蛋白（BMP）信号传导网络能够自发产生周期性图案的能力。使用延时成像，我们发现在毛囊处的间充质细胞凝结是由表皮预模式局部指导的。但是，强加于整个皮肤上的这种具有高FGF和低BMP活性的先验条件表明，在没有上皮方向的情况下，潜在的真皮能力会经历空间模式的自组织。这种间充质的自组织依赖于受限制的转化生长因子（TGF）β信号传导，当抑制反应扩散模式时，它可以驱动趋化性间充质模式，但在正常情况下，可促进细胞向局部预先形成模式的FGF来源移动。这项工作说明了器官发生过程中的周期性模式的层次结构。