Liu Xuena, Li Nan, Zhang Hua, Liu Jing, Zhou Nan, Ran Chunxiao, Chen Xiaoyan, Lu Yongbo, Wang Xiaofang, Qin Chunlin, Xiao Jing, Liu Chao
Department of Radiology, The 2nd Hospital Affiliated to Dalian Medical University, Dalian, Liaoning, China.
Department of Oral Pathology, College of Stomatology, Dalian Medical University, Dalian, Liaoning, China.
Eur J Oral Sci. 2018 Oct;126(5):433-436. doi: 10.1111/eos.12563. Epub 2018 Aug 14.
The glycosaminoglycan (GAG) chains attached to the core proteins of proteoglycans exert multiple roles, such as enriching signal molecules and regulating the binding of ligands to the corresponding receptors. A newly identified kinase - family with sequence similarity 20 member B (FAM20B) - is essential for the formation of GAG chains. The FAM20B protein phosphorylates the initial xylose on the side chain of a serine residue in the protein. Although the GAG chains of proteoglycans are believed to be indispensable during craniofacial development, there are few reports on their exact functions in craniofacial organogenesis. In this study, by mating Wnt1-cre mice with Fam20b-floxed mice (Fam20bflox/flox), we created Wnt1-Cre;Fam20bflox/flox mice in which Fam20b is ablated in the neural crest-derived mesenchyme. The Wnt1-Cre;Fam20bflox/flox mice died immediately after birth because of complete cleft palates. In addition to cleft palate, Wnt1-Cre;Fam20bflox/flox mice also manifested tongue elevation, micrognathia, microcephaly, suture widening, and reduced mineralization in the calvaria, facial bones, and temporomandibular joint. These findings indicate that the proteoglycans formed through the catalysis of FAM20B are essential for the morphogenesis and mineralization of the craniofacial complex.
附着于蛋白聚糖核心蛋白的糖胺聚糖(GAG)链发挥多种作用,例如富集信号分子以及调节配体与相应受体的结合。一种新发现的激酶家族,即序列相似性20成员B(FAM20B),对GAG链的形成至关重要。FAM20B蛋白使蛋白质中丝氨酸残基侧链上的初始木糖磷酸化。尽管蛋白聚糖的GAG链在颅面发育过程中被认为是不可或缺的,但关于它们在颅面器官发生中的确切功能的报道却很少。在本研究中,通过将Wnt1-cre小鼠与Fam20b基因敲除小鼠(Fam20bflox/flox)交配,我们创建了Wnt1-Cre;Fam20bflox/flox小鼠,其中Fam20b在神经嵴衍生的间充质中被敲除。Wnt1-Cre;Fam20bflox/flox小鼠出生后立即死亡,原因是完全腭裂。除腭裂外,Wnt1-Cre;Fam20bflox/flox小鼠还表现出舌抬高、小颌畸形、小头畸形、缝线增宽以及颅盖骨、面骨和颞下颌关节矿化减少。这些发现表明,通过FAM20B催化形成的蛋白聚糖对颅面复合体的形态发生和矿化至关重要。