Lookup NU author(s): Lauren Harkin,
Professor Susan Lindsay,
Dr Yaobo Xu,
Dr Gavin Clowry
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Neurexins (NRXNs) are presynaptic terminal proteins and candidate neurodevelopmental disorder susceptibility genes;mutations presumably upset synaptic stabilization and function. However, analysis of human cortical tissue samples byRNAseq and quantitative real-time PCR at 8–12 postconceptional weeks, prior to extensive synapse formation, showedexpression of all three NRXNs as well as several potential binding partners. However, the levels of expression were notidentical; NRXN1 increased with age and NRXN2 levels were consistently higher than for NRXN3. Immunohistochemistry foreach NRXN also revealed different expression patterns at this stage of development. NRXN1 and NRXN3 immunoreactivitywas generally strongest in the cortical plate and increased in the ventricular zone with age, but was weak in thesynaptogenic presubplate (pSP) and marginal zone. On the other hand, NRXN2 colocalized with synaptophysin in neurites ofthe pSP, but especially with GAP43 and CASK in growing axons of the intermediate zone. Alternative splicing modifies therole of NRXNs and we found evidence by RNAseq for exon skipping at splice site 4 and concomitant expression of KHDBRSproteins which control this splicing. NRXN2 may play a part in early cortical synaptogenesis, but NRXNs could have diverseroles in development including axon guidance, and intercellular communication between proliferating cells and/ormigrating neurons.
Author(s): Harkin LF, Lindsay SJ, Xu Y, Alzu'bi A, Ferrara A, Gullon EA, James OG, Clowry GJ
Publication type: Article
Publication status: Published
Journal: Cerebral Cortex
Online publication date: 24/12/2016
Acceptance date: 02/12/2016
ISSN (print): 1047-3211
ISSN (electronic): 1460-2199
Publisher: Oxford University Press
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