Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice
Defects in limb, craniofacial, and thymic development in Jagged2 mutant mice
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DOI：
10.1101/gad.12.7.1046
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发表时间：
1998-04-01
影响因子：
10.5
通讯作者：
Gridley, T
中科院分区：
文献类型：
--
作者：
Jiang, RL;Lan, Y;Gridley, T
Notch 信号通路是一种保守的细胞间信号传导机制，对于许多后生动物的正常胚胎发育至关重要。我们通过进行靶向突变，去除受体相互作用所需的 Jagged2 蛋白结构域，研究了 Jagged2 (Jag2) 基因的体内作用，该基因编码跨膜受体 Notch 家族的配体。这种缺失的纯合小鼠会因颅面形态发生缺陷而在围产期死亡。突变纯合子表现出腭裂以及舌头与腭架的融合。突变小鼠还表现出前肢和后肢的并指（手指融合）。突变纯合子肢芽的顶端外胚层脊（AER）是增生的，我们观察到AER中Fgf8表达的区域扩大。在突变纯合子的足板中，Bmp2 和 Bmp7 表达以及凋亡指间细胞死亡均减少。突变纯合子还表现出胸腺发育缺陷，表现出胸腺形态改变和γδ谱系T细胞分化受损。这些结果表明，Jag2 介导的 Notch 信号在小鼠四肢、颅面和胸腺发育过程中发挥着重要作用。
The Notch signaling pathway is a conserved intercellular signaling mechanism that is essential for proper embryonic development in numerous metazoan organisms. We have examined the in vivo role of the Jagged2 (Jag2) gene, which encodes a ligand for the Notch family of transmembrane receptors, by making a targeted mutation that removes a domain of the Jagged2 protein required for receptor interaction. Mice homozygous for this deletion die perinatally because of defects in craniofacial morphogenesis. The mutant homozygotes exhibit cleft palate and fusion of the tongue with the palatal shelves. The mutant mice also exhibit syndactyly (digit fusions) of the fore-and hindlimbs. The apical ectodermal ridge (AER) of the limb buds of the mutant homozygotes is hyperplastic, and we observe an expanded domain of Fgf8 expression in the AER. In the foot plates of the mutant homozygotes, both Bmp2 and Bmp7 expression and apoptotic interdigital cell death are reduced. Mutant homozygotes also display defects in thymic development, exhibiting altered thymic morphology and impaired differentiation of gamma delta lineage T cells. These results demonstrate that Notch signaling mediated by Jag2 plays an essential role during limb, craniofacial, and thymic development in mice.