颅骨发育异常是导致颌面部畸形的重要原因，以往的研究发现内分泌蛋白FGF23主要通过调节磷酸盐代谢而影响全身骨发育，对颅骨的影响少有报道。本课题组前期结果显示，FGF23 C35A突变小鼠和Fgf23基因敲除小鼠全身血磷都明显上升，但前者颅缝早闭，后者颅缝闭合不全，提示FGF23可能对颅骨发育存在直接作用。此外，前期RNA-seq、质谱等结果表明发生突变的FGF23蛋白在细胞内大量堆积，并伴随着内质网应激的发生和细胞骨架系统的紊乱。据此，我们提出假说：①FGF23可能通过局部作用直接影响颅骨发育，②FGF23 C35A突变通过内质网应激或改变细胞骨架系统影响细胞的生物学功能，最终导致颅骨发育异常。本课题拟从模式小鼠、细胞生物学、分子生物学三个层次，系统探究FGF23调控颅骨发育的相关机制。研究结果将为颅颌面生长发育的研究提供新的视角，并为先天性颅颌面发育异常的诊断治疗提供新的理论依据。

Dysplasia of cranial bones is one of the most important causes of craniofacial abnormalities. Previous studies have found that the endocrine protein FGF23 affects systemic bone development by regulating phosphate metabolism, however, its impact on cranial bones is rarely reported. Our previous study found that the blood phosphorus level of both FGF23 C35A mutant mice and Fgf23 knockout mice increased significantly, but the former showed craniosynostosis, and the latter showed incomplete cranial suture closure, suggesting that FGF23 may have a direct effect on cranial bone development. In addition, previous RNA-seq, mass spectrometry and other results indicated that the mutant FGF23 protein accumulated in the cells, accompanied by endoplasmic reticulum stress and cytoskeletal abnormalities. Accordingly, we hypothesize that: ① FGF23 may exert regional effect on the development of the cranial bones directly, ② FGF23 C35A mutation affects the biological function of the cells through endoplasmic reticulum stress or interfering the cytoskeleton, which leads to dysplasia of cranial bones. Our study intends to explore the mechanism of FGF23 regulation of cranial bone development from model mice, cell biology and molecular biology. This research will provide a new theoretical basis for the diagnosis and treatment of congenital craniofacial dysplasia.