Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Centre of Excellence in Genomics and Translational Medicine, University of Tartu, 50090 Tartu, Estonia.
Int J Mol Sci. 2021 Jun 28;22(13):6955. doi: 10.3390/ijms22136955.
The members of the IgLON superfamily of cell adhesion molecules facilitate fundamental cellular communication during brain development, maintain functional brain circuitry, and are associated with several neuropsychiatric disorders such as depression, autism, schizophrenia, and intellectual disabilities. Usage of alternative promoter-specific and mRNA isoforms in , , , and the single promoter of in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of , , isoforms, and , in the developing brain, we generated isoform-specific RNA probes and carried out in situ hybridization in the developing (embryonic, E10.5, E11.5, 13.5, 17; postnatal, P0) and adult mouse brains. We show that promoter-specific expression of IgLONs is established early during pallial development (at E10.5), where it remains throughout its differentiation through adulthood. In the diencephalon, midbrain, and hindbrain, strong expression patterns are initiated a few days later and begin fading after birth, being only faintly expressed during adulthood. Thus, the expression of specific IgLONs in the developing brain may provide the means for regionally specific functionality as well as for specific regional vulnerabilities. The current study will therefore improve the understanding of how IgLON genes are implicated in the development of neuropsychiatric disorders.
IgLON 超级家族的细胞粘附分子成员在大脑发育过程中促进基本的细胞通讯，维持功能性大脑回路，并与几种神经精神疾病有关，如抑郁症、自闭症、精神分裂症和智力障碍。先前已经描述了在 、 、 和 中的单一启动子中使用替代启动子特异性和 mRNA 异构体。为了确定 IgLON 、 、 异构体和 在发育中的大脑中的精确时空表达动态，我们生成了异构体特异性 RNA 探针，并在发育中的（胚胎期，E10.5、E11.5、13.5、17；新生期，P0）和成年小鼠脑中进行了原位杂交。我们表明，IgLONs 的启动子特异性表达在大脑皮层发育早期（在 E10.5 时）建立，并且在整个分化过程中一直保持到成年。在间脑、中脑和后脑，强烈的表达模式在几天后开始，并在出生后逐渐消失，在成年期仅微弱表达。因此，特定 IgLONs 在发育中的大脑中的表达可能为区域特异性功能以及特定区域的脆弱性提供了手段。因此，本研究将提高对 IgLON 基因如何参与神经精神疾病发展的理解。
