Tian Ye, Ma Pan, Liu Chao, Yang Xiudong, Crawford Derrick M, Yan Wenjuan, Bai Ding, Qin Chunlin, Wang Xiaofang
Department of Biomedical Sciences and Center for Craniofacial Research and Diagnosis, Texas A&M University Baylor College of Dentistry, Dallas, TX, USA.
Department of Orthodontics, West China School of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Eur J Oral Sci. 2015 Dec;123(6):396-402. doi: 10.1111/eos.12222. Epub 2015 Oct 14.
Tooth formation is tightly regulated by epithelial-mesenchymal interactions via hierarchic cascades of signaling molecules. The glycosaminoglycan (GAG) chains covalently attached to the core protein of proteoglycans (PGs) provide docking sites for signaling molecules and their receptors during the morphogenesis of tissues and organs. Although PGs are believed to play important roles in tooth formation, little is known about their exact functions in this developmental process and the relevant molecular basis. Family with sequence similarity member 20-B (FAM20B) is a newly identified kinase that phosphorylates the xylose in the common linkage region connecting the GAG with the protein core of PGs. The phosphorylation of xylose is essential for elongation of the common linkage region and the subsequent GAG assembly. In this study, we generated a Fam20B-floxed allele in mice and found that inactivating Fam20B in the dental epithelium leads to supernumerary maxillary and mandibular incisors. This finding highlights the pivotal role of PGs in tooth morphogenesis and opens a new window for understanding the regulatory mechanism of PG-mediated signaling cascades during tooth formation.
牙齿形成通过信号分子的层级级联反应由上皮-间充质相互作用严格调控。共价连接到蛋白聚糖（PGs）核心蛋白上的糖胺聚糖（GAG）链在组织和器官形态发生过程中为信号分子及其受体提供对接位点。尽管人们认为PGs在牙齿形成中起重要作用，但对于它们在这个发育过程中的具体功能以及相关分子基础知之甚少。序列相似性家族成员20-B（FAM20B）是一种新发现的激酶，它使连接GAG与PGs蛋白核心的常见连接区域中的木糖磷酸化。木糖的磷酸化对于常见连接区域的延长以及随后的GAG组装至关重要。在本研究中，我们在小鼠中产生了一个Fam20B条件性敲除等位基因，并发现牙上皮中Fam20B的失活会导致上颌和下颌切牙增多。这一发现突出了PGs在牙齿形态发生中的关键作用，并为理解牙齿形成过程中PG介导的信号级联反应的调控机制打开了一扇新窗口。
