Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate.
Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate.
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DOI：
10.3390/ijms24119634
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发表时间：
2023-06-01
影响因子：
5.6
通讯作者：
Liu, Chao
中科院分区：
文献类型：
--
作者：
Chen, Xiaoyan;Li, Nan;Hu, Ping;Li, Leilei;Li, Danya;Liu, Han;Zhu, Lei;Xiao, Jing;Liu, Chao
腭裂是最常见的出生缺陷之一。以往的研究表明，腭裂的发生与细胞内或细胞间信号传导障碍、口腔器官功能失调等多种因素有关，但对细胞外基质（ECM）在腭裂发生中的作用研究较少。蛋白聚糖（PG）是细胞外基质中重要的大分子之一。它们通过一个或多个连接到核心蛋白的糖胺聚糖（GAG）链发挥生物学功能。具有序列相似性的家族20个成员B（Fam 20 B）是新鉴定的激酶磷酸化木糖残基，其通过为GAG链延长创造前提来促进四糖连接区的正确组装。在这项研究中，我们通过Wnt 1-Cre; Fam 20 bf/f小鼠探索了GAG链在腭发育中的功能，这些小鼠表现出完全性腭裂、畸形舌和小颌畸形。Osr2-Cre; Fam 20 bf/f小鼠，其中Fam 20 b仅在腭间充质中缺失，未显示异常，表明Wnt 1-Cre; Fam 20 bf/f小鼠中腭提升失败是继发于小颌畸形。此外，减少的GAG链促进腭细胞的凋亡，主要导致细胞密度降低和腭体积减小。BMP信号的抑制和矿化的减少表明腭骨的成骨受损，这可以通过组成性活性Bmpr 1a部分地拯救。总之，我们的研究强调了GAG链在腭形态发生中的关键作用。
Cleft palate is one of the most common birth defects. Previous studies revealed that multiple factors, including impaired intracellular or intercellular signals, and incoordination of oral organs led to cleft palate, but were little concerned about the contribution of the extracellular matrix (ECM) during palatogenesis. Proteoglycans (PGs) are one of the important macromolecules in the ECM. They exert biological functions through one or more glycosaminoglycan (GAG) chains attached to core proteins. The family with sequence similarity 20 member b (Fam20b) are newly identified kinase-phosphorylating xylose residues that promote the correct assembly of the tetrasaccharide linkage region by creating a premise for GAG chain elongation. In this study, we explored the function of GAG chains in palate development through Wnt1-Cre; Fam20bf/f mice, which exhibited complete cleft palate, malformed tongue, and micrognathia. In contrast, Osr2-Cre; Fam20bf/f mice, in which Fam20b was deleted only in palatal mesenchyme, showed no abnormality, suggesting that failed palatal elevation in Wnt1-Cre; Fam20bf/f mice was secondary to micrognathia. In addition, the reduced GAG chains promoted the apoptosis of palatal cells, primarily resulting in reduced cell density and decreased palatal volume. The suppressed BMP signaling and reduced mineralization indicated an impaired osteogenesis of palatine, which could be rescued partially by constitutively active Bmpr1a. Together, our study highlighted the key role of GAG chains in palate morphogenesis.
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影响因子：
5.6
作者：
Amarasekara DS;Kim S;Rho J
通讯作者：
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DOI：
10.1016/j.ijporl.2019.109842
发表时间：
2020-04-01
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