Monavarfeshani Aboozar, Knill Courtney N, Sabbagh Ubadah, Su Jianmin, Fox Michael A
Developmental and Translational Neurobiology Center, Virginia Tech Carilion Research InstituteRoanoke, VA, United States.
Department of Biological Sciences, Virginia TechBlacksburg, VA, United States.
Front Integr Neurosci. 2017 Aug 30;11:20. doi: 10.3389/fnint.2017.00020. eCollection 2017.
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 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 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.
非传统胶原蛋白是一类非纤维状蛋白质,它们不仅对细胞外基质的结构有贡献,还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所起的作用已得到充分证实,但直到最近,研究才确定这些蛋白质在大脑发育中的作用,更具体地说,是在神经元之间突触连接的形成和完善过程中的作用。然而,我们对哺乳动物大脑中产生的完整非传统胶原蛋白种类的了解仍然不清楚。在这里,我们试图通过评估跨膜胶原蛋白(即胶原蛋白 XIII、XVII、XXIII 和 XXV)在小鼠大脑中的表达来填补这一空白。通过定量 PCR 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。对于两种表达量最高的跨膜胶原蛋白(即胶原蛋白 XXIII 和 XXV),我们证明它们由大脑不同部位的特定神经元亚群表达。例如,胶原蛋白 XXIII 由副嗅球(AOB)的二尖瓣/簇状细胞层中的兴奋性神经元以及视网膜内核层(INL)中的细胞选择性表达。另一方面,表达更为广泛的胶原蛋白 XXV 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。其表达不仅存在于视网膜中,而且在大脑内的视网膜接受核(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)中似乎特别富集。综上所述,跨膜胶原蛋白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。