Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development.
Delta-like 1 regulates Bergmann glial monolayer formation during cerebellar development.
复制标题
小脑发育过程中，三角洲的1调节伯格曼神经胶质单层形成。
DOI：
10.1186/1756-6606-6-25
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发表时间：
2013-05-21
期刊：
影响因子：
3.6
通讯作者：
Tanaka K
中科院分区：
文献类型：
--
作者：
Hiraoka Y;Komine O;Nagaoka M;Bai N;Hozumi K;Tanaka K
伯格曼胶质细胞（BG）是单极小脑星形胶质细胞。成熟BG的体驻留在浦肯野细胞层内，呈放射状向脑柱面延伸。BG具有多个分支突起，这些分支突起包裹着浦肯野细胞树突的突触。它们在发育过程中从心室区迁移到浦肯野细胞层附近。此前，我们报道了BG中的Notch1、Notch2和RBPj基因在BG的单层形成和形态发生中起着至关重要的作用。然而，究竟是哪一种配体激活了BG上的notth1和Notch 2，尚不清楚。Delta-like 1 （Dll1）是Notch受体的主要配体，在发育中的小脑中表达。在这项研究中，我们使用人类胶质纤维酸性蛋白（hGFAP）启动子驱动的cre介导重组来删除BG中的Dll1。dll1条件突变小鼠表现为伯格曼纤维紊乱，BG在分子层异位，BG数量减少。这些结果表明，Dll1是BG层形成及其形态成熟所必需的，显然是通过Notch1/2-RBPj依赖的信号通路。
Bergmann glia (BG) are unipolar cerebellar astrocytes. The somata of mature BG reside in the Purkinje cell layer and extend radially arranged processes to the pial surface. BG have multiple branched processes, which enwrap the synapses of Purkinje cell dendrites. They migrate from the ventricular zone and align next to the Purkinje cell layer during development. Previously, we reported that Notch1, Notch2, and RBPj genes in the BG play crucial roles in the monolayer formation and morphogenesis of BG. However, it remains to be determined which ligand activates Nocth1 and Notch 2 on BG. Delta-like 1 (Dll1) is a major ligand of Notch receptors that is expressed in the developing cerebellum. In this study, we used human glial fibrillary acidic protein (hGFAP) promoter-driven Cre-mediated recombination to delete Dll1 in BG. Dll1-conditional mutant mice showed disorganization of Bergmann fibers, ectopic localization of BG in the molecular layer and a reduction in the number of BG. These results suggest that Dll1 is required for the formation of the BG layer and its morphological maturation, apparently through a Notch1/2-RBPj dependent signaling pathway.
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