The Xenopus Model as a Tool for Investigating Craniofacial Developmental Disorders

Qianying Kong^1,2,3,4Huifang Peng¹Qian Zhao^1,2,3,4Hongwei Jiang^1*Xuechen Zhu^3,4,5*

• ¹The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China
• ²State Key Laboratory of Female Fertility Promotion, Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
• ³Department of Pediatrics, Children's Medical Center, Peking University First Hospital, Beijing, China
• ⁴Neuroscience Research Institute, Peking University, Beijing, China
• ⁵State Key Laboratory of Female Fertility Promotion, Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center,, Beijing, China

Normal craniofacial development depends on the precise specification, migration, and differentiation of cranial neural crest cells (CNCCs). Perturbations in these processes result in a wide spectrum of congenital craniofacial anomalies, which represent a major cause of birth defects worldwide. Xenopus has emerged as a particularly powerful model for investigating craniofacial morphogenesis, owing to its external fertilization, large and experimentally accessible embryos, and evolutionarily conserved developmental pathways. These advantages allow direct in vivo visualization and manipulation of CNCCs behaviors at single-cell resolution, providing opportunities not readily achievable in mammalian models. With the integration of advanced techniques such as high-resolution imaging, lineage tracing, microsurgical manipulation, and genome editing, the utility of Xenopus in craniofacial biology has been greatly expanded. In this review, we outline the key stages of craniofacial development, summarize representative craniofacial developmental disorders studied using Xenopus as a model, and highlight how this system has provided critical mechanistic insights. Importantly, the amenability of Xenopus embryos to small-molecule screening underscores their translational potential as a rapid preclinical platform, linking human genetic variants to disease pathogenesis and accelerating therapeutic discovery for craniofacial disorders, as well as its translational potential as a rapid preclinical platform, linking human genetic variants to disease pathogenesis and accelerating therapeutic discovery for craniofacial disorders.