Abstract
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 1a and 1b mRNA isoforms in Lsamp, Opcml, Ntm, and the single promoter of Negr1 in the mouse and human brain has been previously described. To determine the precise spatiotemporal expression dynamics of Lsamp, Opcml, Ntm isoforms, and Negr1, 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.
Highlights
The first sign of vertebrate brain development is the appearance of the neural plate, which gives rise to neuroepithelial cells (NECs), the precursors of neural progenitor cells (NPCs)
The first sign of the expression of Lsamp, Negr1, Ntm, and Opcml in the central nervous system (CNS) coincided in mid gestational stages, at the time when active neurogenesis and neuronal migration occurs
Prior to the neuroepithelium entering its massive neurogenesis phase at E10.5, expression is already observable for Lsamp 1a, Negr1, Ntm 1a, and Opcml 1b in the neural tube, ventricular zone, and around the ventricular vesicles (Supplementary Figure S1)
Summary
The first sign of vertebrate brain development is the appearance of the neural plate, which gives rise to neuroepithelial cells (NECs), the precursors of neural progenitor cells (NPCs). Histogenetic processes of neural tissue formation encompasses massive proliferation and migration of progenitor cells, followed by neuronal differentiation together with neuritogenesis and axon guidance to appropriate targets for creating synaptic connections [1,2,3]. These processes are highly coordinated by spatiotemporal crosstalk of signaling cues and gene regulatory pathways, accounting for proteome diversifications by generating multiple alternative mRNA isoforms [4,5,6,7]. Differences in cognitive ability have been associated with NEGR1 [32] and the loci of all IgLONs significantly associate with the educational attainment [33]
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