State Key Laboratory of Genetic Engineering, Institute of Genetics, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai 200438, China.
State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
J Cell Sci. 2018 May 29;131(10):jcs210781. doi: 10.1242/jcs.210781.
Heparan sulfate proteoglycans (HSPGs) have been shown to regulate various developmental processes. However, the function of heparan sulfate (HS) during the development of mammalian stomach has not been characterized yet. Here, we investigate the role of epithelial HS in embryonic stomach by examining mice deficient in the glycosyltransferase gene We show that HS exhibits a specific and dynamic expression pattern in mouse embryonic stomach. Depletion of the epithelial HS leads to stomach hypoplasia, with phenotypic differences in the gastric mucosa between the forestomach and hindstomach. In the posterior stomach, HS depletion disrupts glandular stomach patterning and cytodifferentiation via attenuation of Fgf signaling activity. Inhibition of Fgf signaling recapitulates the patterning defect. Ligand and carbohydrate engagement assay (LACE) reveals a diminished assembly of Fgf10 and Fgfr2b in the mutant. In the anterior stomach, loss of epithelial HS leads to stratification and differentiation defects of the multilayered squamous epithelium, along with reduced Hh and Bmp signaling activity. Our data demonstrate that epithelial HS plays multiple roles in regulating mammalian stomach morphogenesis in a regional-specific manner.
硫酸乙酰肝素蛋白聚糖（HSPGs）已被证明能调节多种发育过程。然而，在哺乳动物胃的发育过程中，硫酸乙酰肝素（HS）的功能尚未被描述。在这里，我们通过研究糖苷转移酶基因缺失的小鼠，研究了上皮细胞 HS 在胚胎胃发育中的作用。我们发现 HS 在小鼠胚胎胃中呈现出特异性和动态的表达模式。上皮细胞 HS 的耗竭导致胃发育不良，前胃和后胃的胃黏膜表现出不同的表型。在后胃中，HS 的耗竭通过减弱 Fgf 信号活性破坏了腺胃的模式形成和细胞分化。Fgf 信号的抑制可以重现模式形成缺陷。配体和碳水化合物结合分析（LACE）显示突变体中 Fgf10 和 Fgfr2b 的组装减少。在前胃中，上皮细胞 HS 的缺失导致多层鳞状上皮的分层和分化缺陷，同时 Hh 和 Bmp 信号活性降低。我们的数据表明，上皮细胞 HS 以区域特异性的方式在调节哺乳动物胃形态发生中发挥多种作用。
