Characterization of Notch receptor expression in the developing mammalian heart and liver
Characterization of Notch receptor expression in the developing mammalian heart and liver
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DOI：
10.1002/ajmg.10592
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发表时间：
2002-10-01
期刊：
影响因子：
--
通讯作者：
Oakey, RJ
中科院分区：
文献类型：
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作者：
Loomes, KM;Taichman, DB;Oakey, RJ
Alagille综合征（AGS）是一种常染色体显性遗传疾病，其特征是胆管缺乏沿着心血管、骨骼和眼科缺陷。JAG 1作为AGS疾病基因的鉴定揭示了Notch信号通路在人类多器官系统发育中的关键作用。在JAG 1中具有相同突变的患者表现出极端的临床变异性，这表明其他因素可能会影响这种疾病中发育缺陷的严重程度。我们已经定义了Notch受体基因在发育中的哺乳动物心脏和肝脏的时间和空间表达模式，以确定潜在的配体/受体在胚胎发生过程中的相互作用。在发育中的心脏中，Notch 1和Notch 2都在流出道和心外膜中表达，在先前显示表达JAG 1的特定细胞群中。这些细胞注定要经历上皮-间充质转化。在新生小鼠肝脏中，Notch 2和Notch 3在相反的细胞群中表达，表明它们在胆管发育期间的细胞命运决定中发挥不同的作用。JAG 1也在与表达Notch 2的细胞相邻的细胞中表达，表明可能的配体受体关系。Notch受体在不同器官系统中的细胞命运决定中具有不同的作用。(C)2002 Wiley-Liss，Inc.
Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile duct paucity along with cardiovascular, skeletal, and ophthalmologic defects. The identification of JAG1 as the AGS disease gene revealed the crucial role of the Notch signaling pathway in the development of multiple organ systems in humans. Patients with identical mutations in JAG1 demonstrate extreme clinical variability, suggesting that other factors may influence the severity of the developmental defects in this disorder. We have defined the temporal and spatial expression patterns of the Notch receptor genes in the developing mammalian heart and liver in order to identify potential ligand/receptor interactions during embryogenesis. In the developing heart, both Notch1 and Notch2 are expressed in the outflow tracts and the epicardium, in specific cell populations previously shown to express JAG1. These cells are destined to undergo epithelial-to-mesenchymal transformation. In the newborn mouse liver, Notch2 and Notch3 are expressed in opposing cell populations, suggesting they play different roles in cell fate determination during bile duct development. JAG1 is also expressed in cells adjacent to those expressing Notch2, suggesting a possible ligand receptor relationship. The Notch receptors have distinct roles in cell fate determination in different organ systems. (C) 2002 Wiley-Liss, Inc.