Region- and Cell-Specific Expression of Transmembrane Collagens in Mouse Brain.

Region- and Cell-Specific Expression of Transmembrane Collagens in Mouse Brain.
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DOI:
10.3389/fnint.2017.00020
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发表时间:
2017
影响因子:
3.5
通讯作者:
Fox MA
Fox MA
中科院分区:
医学3区
文献类型:
--
作者:
Monavarfeshani A;Knill CN;Sabbagh U;Su J;Fox MA

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非传统胶原蛋白是一种非纤维蛋白,不仅对细胞外基质的结构有贡献,而且具有独特的生物活性。尽管非传统胶原蛋白在非神经组织的发育和功能中的作用已经得到了很好的证实,但直到最近才有研究确定这些蛋白在大脑发育中的作用,更具体地说,在神经元之间突触连接的形成和完善方面。尽管如此,我们对哺乳动物大脑中产生的非传统胶原蛋白的完整队列的理解仍然不清楚。在这里,我们试图通过评估跨膜胶原(即XIII、XVII、XXIII和XXV)在小鼠脑中的表达来解决这一差距。利用定量聚合酶链式反应和原位杂交(ISH),我们证明了这些独特的胶原蛋白在发育中的大脑中具有区域和细胞特异性表达。对于两种表达最高的跨膜胶原蛋白(即XXIII和XXV胶原蛋白),我们证明它们在大脑不同部分的特定神经元亚群中表达。例如,XXIII型胶原由副嗅球(AOB)二尖瓣/簇状细胞层的兴奋性神经元和视网膜内核层(INL)的细胞选择性表达。另一方面,更广泛表达的XXV胶原是由背侧丘脑和中脑的兴奋性神经元亚群以及视网膜、腹侧丘脑和端脑的抑制性神经元产生的。Col25a1不仅存在于视网膜中,而且在大脑内的视网膜受体核(包括视交叉上核(SCN)、外侧膝状体复合体、橄榄顶盖前核(OPN)和上丘)中似乎特异性地丰富。综上所述,跨膜胶原独特的区域和细胞特异性表达模式表明,这一非传统胶原蛋白家族可能在大脑发育和功能中发挥独特的、尚未确定的作用。
Unconventional collagens are nonfribrillar proteins that not only contribute to the structure of extracellular matrices but exhibit unique bio-activities. Although roles for unconventional collagens have been well-established in the development and function of non-neural tissues, only recently have studies identified roles for these proteins in brain development, and more specifically, in the formation and refinement of synaptic connections between neurons. Still, our understanding of the full cohort of unconventional collagens that are generated in the mammalian brain remains unclear. Here, we sought to address this gap by assessing the expression of transmembrane collagens (i.e., collagens XIII, XVII, XXIII and XXV) in mouse brain. Using quantitative PCR and in situ hybridization (ISH), we demonstrate both region- and cell-specific expression of these unique collagens in the developing brain. For the two most highly expressed transmembrane collagens (i.e., collagen XXIII and XXV), we demonstrate that they are expressed by select subsets of neurons in different parts of the brain. For example, collagen XXIII is selectively expressed by excitatory neurons in the mitral/tufted cell layer of the accessory olfactory bulb (AOB) and by cells in the inner nuclear layer (INL) of the retina. On the other hand, collagen XXV, which is more broadly expressed, is generated by subsets of excitatory neurons in the dorsal thalamus and midbrain and by inhibitory neurons in the retina, ventral thalamus and telencephalon. Not only is col25a1 expression present in retina, it appears specifically enriched in retino-recipient nuclei within the brain (including the suprachiasmatic nucleus (SCN), lateral geniculate complex, olivary pretectal nucleus (OPN) and superior colliculus). Taken together, the distinct region- and cell-specific expression patterns of transmembrane collagens suggest that this family of unconventional collagens may play unique, yet-to-be identified roles in brain development and function.
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