Mind the gap: genetic manipulation of basicranial growth within synchondroses modulates calvarial and facial shape in mice through epigenetic interactions

Phenotypic integration patterns in the mammalian skull have long been a focus of intense interest as a result of their suspected influence on the trajectory of hominid evolution. Here we test the hypothesis that perturbation of cartilage growth, which directly affects only the chondrocranium during development, will produce coordinated shape changes in the adult calvarium and face regardless of mechanism. Using two murine models of cartilage undergrowth that target two very different mechanisms, we show that strong reduction in cartilage growth produces a short, wide, and more flexed cranial base. This in turn produces a short, wide face in both models. Cranial base and face are already correlated early in ontogeny, and the relationship between these modules gains structure through postnatal growth and development. These results provide further evidence that there exist physical interactions between developing parts of the phenotype that produce variation at a distance from the actual l...哺乳动物颅骨的表型整合模式（phenotypic integration）长期以来均为学界高度关注的研究热点，因其被推测可影响人科（hominid）的演化路径。本研究检验下述假说：软骨生长（cartilage growth）的扰动仅在发育阶段直接作用于软骨颅（chondrocranium），无论其作用机制为何，均可促使成年个体颅盖骨（calvarium）与面部产生协同形态变化。本研究采用两种靶向不同作用机制的软骨发育不全小鼠模型，证实软骨生长的显著抑制会导致颅底变短、增宽且弯曲度更高。这一变化进而在两个模型中均引发面部变短、增宽的表型。颅底与面部在个体发育（ontogeny）早期便已存在相关性，二者作为发育模块间的关联会随着出生后的生长发育逐步构建出特定结构。上述结果进一步证实，表型发育的不同组分之间存在物理相互作用，可在远离实际作用位点的位置产生表型变异……