Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania, United States of America.
PLoS One. 2011;6(10):e26425. doi: 10.1371/journal.pone.0026425. Epub 2011 Oct 28.
The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorphology of the skull, brain and limbs, among other organs. Since this molecular pathway is widely expressed throughout head development, we explore whether and how two specific mutations on Fgfr2 causing Apert syndrome in humans affect the pattern and level of integration between the facial skeleton and the neurocranium using inbred Apert syndrome mouse models Fgfr2(+/S252W) and Fgfr2(+/P253R) and their non-mutant littermates at P0. Skull morphological integration (MI), which can reflect developmental interactions among traits by measuring the intensity of statistical associations among them, was assessed using data from microCT images of the skull of Apert syndrome mouse models and 3D geometric morphometric methods. Our results show that mutant Apert syndrome mice share the general pattern of MI with their non-mutant littermates, but the magnitude of integration between and within the facial skeleton and the neurocranium is increased, especially in Fgfr2(+/S252W) mice. This indicates that although Fgfr2 mutations do not disrupt skull MI, FGF/FGFR signaling is a covariance-generating process in skull development that acts as a global factor modulating the intensity of MI. As this pathway evolved early in vertebrate evolution, it may have played a significant role in establishing the patterns of skull MI and coordinating proper skull development.
成纤维细胞生长因子及其受体系统（FGF/FGFR）介导许多组织类型的细胞通讯和形态发生（例如，骨骼、神经、血管）。在 FGFR1-3 突变引起的颅缝早闭综合征中，FGF/FGFR 系统信号的改变导致颅骨、大脑和四肢等其他器官的畸形。由于该分子途径在头部发育过程中广泛表达，我们探讨了导致人类 Apert 综合征的 Fgfr2 上的两个特定突变是否以及如何影响面部骨骼和神经颅之间的模式和整合水平，使用近交 Apert 综合征小鼠模型 Fgfr2(+/S252W)和 Fgfr2(+/P253R)及其非突变同窝仔鼠在 P0 时。颅骨形态整合（MI）可以通过测量它们之间统计关联的强度来反映性状之间的发育相互作用，我们使用 Apert 综合征小鼠模型的颅骨 microCT 图像和 3D 几何形态测量方法的数据来评估 MI。我们的结果表明，突变型 Apert 综合征小鼠与非突变同窝仔鼠具有相同的 MI 模式，但面部骨骼和神经颅之间和内部的整合程度增加，尤其是在 Fgfr2(+/S252W)小鼠中。这表明，尽管 Fgfr2 突变不会破坏颅骨 MI，但 FGF/FGFR 信号是颅骨发育中的协方差生成过程，作为调节 MI 强度的全局因素。由于该途径在脊椎动物进化的早期就已经进化，因此它可能在建立颅骨 MI 模式和协调适当的颅骨发育方面发挥了重要作用。
