JAGGED1 gene expression during human embryogenesis elucidates the wide phenotypic spectrum of Alagille syndrome
JAGGED1 gene expression during human embryogenesis elucidates the wide phenotypic spectrum of Alagille syndrome
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DOI：
10.1053/jhep.2000.16600
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发表时间：
2000-09-01
期刊：
影响因子：
13.5
通讯作者：
Vekemans, M
中科院分区：
文献类型：
--
作者：
Crosnier, C;Attié-Bitach, T;Vekemans, M
编码NOTCH受体配体的JAGGED1基因发生突变会导致阿拉杰里综合征（AGS），这是一种主要影响肝脏、心脏、脊椎、眼睛和面部的复杂畸形疾病。在某些病例中，涉及肾脏、咽部、全身动脉、骨骼和耳朵的次要及偶发特征也与该综合征有关。为了描述JAGGED1在人类胚胎发生过程中的表达情况，并研究其与AGS所有特征的关系，我们对人类胚胎和胎儿组织切片进行了原位杂交研究。JAGGED1主要在心血管系统中表达。在肝脏中，仅在血管中检测到JAGGED1转录本。JAGGED1还在其他间充质来源的结构（肢芽的远端间充质；肾脏的中肾和后肾小管）以及上皮结构中表达，包括视网膜的睫状缘和晶状体后部、耳囊的腹侧上皮、耳前庭的神经感觉上皮、咽弓的上皮以及发育中的中枢神经系统。在人类胚胎和胎儿发生过程中，JAGGED1在血管系统以及其他间充质和上皮组织中的强烈表达表明异常血管生成在阿拉杰里综合征的发病机制中起作用，特别是在小叶间胆管稀少这一方面。然而，这可能不是该疾病的唯一发病机制。除了中枢神经系统外，JAGGED1的表达与AGS的所有特征之间存在很强的相关性。这意味着偶尔与该综合征相关的特征并非偶然。
Mutations of the JAGGED1 gene, encoding a NOTCH receptor ligand, cause Alagille syndrome (AGS), a complex malformative disorder affecting mainly the liver, heart, vertebrae, eye, and face. Minor and occasional features involving kidney, pharynx, systemic arteries, skeleton, and ear are in some cases associated with the syndrome. To describe the expression of JAGGED1 during human embryogenesis and to study its relationship with all the features of AGS, we performed in situ hybridization studies on human embryos and fetal tissue sections. JAGGED1 was mainly expressed in the cardiovascular system. In the liver, JAGGED1 transcripts were only detected in blood vessels. JAGGED1 was also expressed in other structures of mesenchymal origin (distal mesenchyme of limb buds; mesonephric and metanephric tubules of the kidney) and in epithelial structures including the ciliary margin of the retina and the posterior part of the lens, the ventral epithelium of the otic vesicle, the neurosensory epithelium of the ear vestibule, the epithelium of pharyngeal arches, and the developing central nervous system. The strong JAGGED1 expression during human embryo- and fete-genesis both in the vascular system and in other mesenchymal and epithelial tissues implicates abnormal angiogenesis in the pathogenesis of Alagille syndrome and particularly the paucity of interlobular bile ducts. However, it is probably not the only mechanism of the disease. Except for the central nervous system, there is a strong correlation between JAGGED1 expression and all the features of AGS. This implies that the features occasionally associated with the syndrome are not coincidental.