Boggild Simon, Molgaard Simon, Glerup Simon, Nyengaard Jens Randel
Department of Clinical Medicine, Aarhus University, MIND Centre, Core Center for Molecular Morphology, Section for Stereology and Microscopy, Aarhus C, 8000, Denmark.
MIND Centre, Department of Biomedicine, Aarhus University, Ole Worms Allé 3, Aarhus C, 8000, Denmark.
J Comp Neurol. 2018 Jun 1;526(8):1267-1286. doi: 10.1002/cne.24403. Epub 2018 Feb 20.
Nervous system development is a precisely orchestrated series of events requiring a multitude of intrinsic and extrinsic cues. Sortilin and SorCS2 are members of the Vps10p receptor family with complementary influence on some of these cues including the neurotrophins (NTs). However, the developmental time points where sortilin and SorCS2 exert their activities in conjunction or independently still remain unclear. In this study we present the characterization of the spatiotemporal expression pattern of sortilin and SorCS2 in the developing murine nervous system. Sortilin is highly expressed in the fetal nervous system with expression localized to distinct cell populations. Expression was high in neurons of the cortical plate and developing allocortex, as well as subpallial structures. Furthermore, the neuroepithelium lining the ventricles and the choroid plexus showed high expression of sortilin, together with the developing retina, spinal ganglia, and sympathetic ganglia. In contrast, SorCS2 was confined in a marked degree to the thalamus and, at E13.5, the floor plate from midbrain rostrally to spinal cord caudally. SorCS2 was also found in the ventricular zones of the ventral hippocampus and nucleus accumbens areas, in the meninges and in Schwann cells. Hence, sortilin and SorCS2 are extensively present in several distinct anatomical areas in the developing nervous system and are rarely co-expressed. Possible functions of sortilin and SorCS2 pertain to NT signaling, axon guidance and beyond. The present data will form the basis for hypotheses and study designs for unravelling the functions of sortilin and SorCS2 during the establishment of neuronal structures and connections.
神经系统发育是一系列精确编排的事件，需要众多内在和外在信号。Sortilin和SorCS2是Vps10p受体家族成员，对包括神经营养因子（NTs）在内的一些信号具有互补影响。然而，Sortilin和SorCS2协同或独立发挥作用的发育时间点仍不清楚。在本研究中，我们描述了Sortilin和SorCS2在发育中的小鼠神经系统中的时空表达模式。Sortilin在胎儿神经系统中高度表达，表达定位于不同的细胞群体。在皮质板和发育中的allocortex的神经元以及皮质下结构中表达很高。此外，脑室和脉络丛内衬的神经上皮与发育中的视网膜、脊髓神经节和交感神经节一起显示出Sortilin的高表达。相比之下，SorCS2在很大程度上局限于丘脑，在E13.5时，从脑桥中部到脊髓尾部的底板也有表达。在腹侧海马体和伏隔核区域的脑室区、脑膜和雪旺细胞中也发现了SorCS2。因此，Sortilin和SorCS2广泛存在于发育中的神经系统的几个不同解剖区域，很少共表达。Sortilin和SorCS2的可能功能与NTs信号传导、轴突导向等有关。目前的数据将为阐明Sortilin和SorCS2在神经元结构和连接建立过程中的功能的假设和研究设计奠定基础。
