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Neurexins 1–3 Each Have a Distinct Pattern of Expression in the Early Developing Human Cerebral Cortex

Lookup NU author(s): Lauren Harkin, Professor Susan Lindsay, Dr Yaobo Xu, Ayman Alzu'bi, Dr Gavin Clowry

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

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

Year: 2017

Volume: 27

Issue: 1

Pages: 216-232

Online publication date: 24/12/2016

Acceptance date: 02/12/2016

ISSN (print): 1047-3211

ISSN (electronic): 1460-2199

Publisher: Oxford University Press

URL: https://doi.org/10.1093/cercor/bhw394

DOI: 10.1093/cercor/bhw394


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