Sharaf Ahmed, Rahhal Belal, Spittau Björn, Roussa Eleni
Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Albert-Ludwigs-University Freiburg, Albertstrasse 17, 79104, Freiburg, Germany.
Department of Histology and Cytology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt.
Cell Tissue Res. 2015 Feb;359(2):393-407. doi: 10.1007/s00441-014-2022-6. Epub 2014 Nov 25.
We investigated the distribution patterns of the extracellular matrix protein Reelin and of crucial Reelin signaling components in murine midbrain and striatum. The cellular distribution of the Reelin receptors VLDLr and ApoER2, the intracellular downstream mediator Dab1, and the alternative Reelin receptor APP were analyzed at embryonic day 16, at postnatal stage 15 (P15), and in 3-month-old mice. Reelin was expressed intracellularly and extracellularly in midbrain mesencephalic dopaminergic (mDA) neurons of newborns. In the striatum, Calbindin D-28k(+) neurons exhibited Reelin intracellularly at E16 and extracellularly at P15 and 3 months. ApoER2 and VLDLr were expressed in mDA neurons at E16 and P15 and in oligodendrocytes at 3 months, whereas Dab1 and APP immunoreactivity was observed in mDA at all stages analyzed. In the striatum, Calbindin D-28k(+)/GAD67(+) inhibitory neurons expressed VLDLr, ApoER2, and Dab1 at P15, but only Dab1 at E16 and 3 months. APP was always expressed in mouse striatum in which it colocalized with Calbindin D-28k. Our data underline the importance of Reelin signalling during embryonic development and early postnatal maturation of the mesostriatal and mesocorticolimbic system, and suggest that the striatum and not the midbrain is the primary source of Reelin for midbrain neurons. The loss of ApoER2 and VLDLr expression in the mature midbrain and striatum implies that Reelin functions are restricted to migratory events and early postnatal maturation and are dispensable for the maintenance of dopaminergic neurons.
我们研究了细胞外基质蛋白Reelin以及关键的Reelin信号传导成分在小鼠中脑和纹状体中的分布模式。在胚胎第16天、出生后第15阶段(P15)以及3月龄小鼠中,分析了Reelin受体VLDLr和ApoER2、细胞内下游介质Dab1以及替代性Reelin受体APP的细胞分布。Reelin在新生小鼠中脑的中脑多巴胺能(mDA)神经元的细胞内和细胞外均有表达。在纹状体中,钙结合蛋白D - 28k(+)神经元在E16时细胞内表达Reelin,在P15和3个月时细胞外表达Reelin。ApoER2和VLDLr在E16和P15时在mDA神经元中表达,在3个月时在少突胶质细胞中表达,而在所有分析阶段的mDA中均观察到Dab1和APP免疫反应性。在纹状体中,钙结合蛋白D - 28k(+)/GAD67(+)抑制性神经元在P15时表达VLDLr、ApoER2和Dab1,但在E16和3个月时仅表达Dab1。APP始终在小鼠纹状体中表达,并与钙结合蛋白D - 28k共定位。我们的数据强调了Reelin信号在胚胎发育以及中脑纹状体和中脑皮质边缘系统出生后早期成熟过程中的重要性,并表明纹状体而非中脑是中脑神经元Reelin的主要来源。成熟中脑和纹状体中ApoER2和VLDLr表达的缺失意味着Reelin功能仅限于迁移事件和出生后早期成熟,对于多巴胺能神经元的维持并非必需。