Alternative Promoter Use Governs the Expression of IgLON Cell Adhesion Molecules in Histogenetic Fields of the Embryonic Mouse Brain

• Main Authors: Toomas Jagomäe, Katyayani Singh, Mari-Anne Philips, Mohan Jayaram, Kadri Seppa, Triin Tekko, Scott F. Gilbert, Eero Vasar, Kersti Lilleväli
• Format: Article
• Language: English
• Published: MDPI AG 2021-06-01
• Series: International Journal of Molecular Sciences
• Subjects: IgLON; <i>Lsamp</i>; <i>Ntm</i>; <i>Opcml</i>; <i>Negr1</i>; alternative promoter
• Online Access: https://www.mdpi.com/1422-0067/22/13/6955
• ISSN: 1661-6596; 1422-0067

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 <i>1a</i> and <i>1b</i> mRNA isoforms in <i>Lsamp</i>, <i>Opcml</i>, <i>Ntm</i>, and the single promoter of <i>Negr1</i> in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of <i>Lsamp</i>, <i>Opcml</i>, <i>Ntm</i> isoforms, and <i>Negr1</i>, 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.