Jagged1 ablation results in cerebellar granule cell migration defects and depletion of Bergmann glia
Jagged1 ablation results in cerebellar granule cell migration defects and depletion of Bergmann glia
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DOI：
10.1159/000090754
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发表时间：
2006-01-01
影响因子：
2.9
通讯作者：
Taylor, V
中科院分区：
文献类型：
--
作者：
Weller, M;Krautler, N;Taylor, V
Jagged1是Notch受体家族成员的配体。人类JAG1基因突变是Alagille综合征的主要原因，Alagille综合征是一种影响肝脏、心脏、眼睛、骨骼、肾脏和颅面结构的常染色体显性遗传疾病。尽管Jagged1在哺乳动物胚胎发育和成年期均有表达，但其在中枢神经系统中的功能尚不清楚。Jagged1在小脑中广泛表达，表明其在Notch信号传导中起重要作用。为了研究Jagged1在小鼠中枢神经系统中的功能，我们在胚胎中期的小脑原基中失活了Jag1基因。Jagged1基因缺失导致出生后早期小脑外胚层和分子层颗粒细胞迁移和异位分化异常。我们发现，伯格曼胶质细胞在小脑失去了软脑膜表面的接触，并有发育不良的过程。体外分析显示，在Jagged1突变小鼠的伯格曼神经胶质细胞的耗竭。我们的研究结果表明，锯齿状蛋白1在小脑细胞命运的规范和生存中发挥作用。
Jagged1 is a ligand for members of the Notch family of receptors. Mutations in the human JAG1 gene are the major cause of Alagille syndrome, an autosomal dominant disorder affecting the liver, heart, eye, skeleton, kidneys, and craniofacial structures. Although expressed throughout mammalian embryonic development and in the adult, the function of Jagged1 in the central nervous system is not clear. Jagged1 is broadly expressed in the cerebellum suggesting an important role in Notch signaling. In order to address the function of Jagged1 in the mouse central nervous system, we have inactivated the Jag1 gene in the cerebellar primordium at mid-embryogenesis. Loss of Jagged1 results in aberrant granule cell migration and ectopic differentiation in the external germinal layer and molecular layer of the early postnatal cerebellum. We show that Bergmann glia in the cerebellum lose contact to the pial surface and have stunted processes. In vitro analysis revealed a depletion of Bergmann glia in the Jagged1 mutant mice. Our findings suggest that Jagged1 plays a role in cell fate specification and survival in the cerebellum.