title: Neurexins 1-3 Each Have a Distinct Pattern of Expression in the Early Developing Human Cerebral Cortex.
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 by RNAseq and quantitative real-time PCR at 8-12 postconceptional weeks, prior to extensive synapse formation, showed expression of all three NRXNs as well as several potential binding partners. However, the levels of expression were not identical; NRXN1 increased with age and NRXN2 levels were consistently higher than for NRXN3. Immunohistochemistry for each NRXN also revealed different expression patterns at this stage of development. NRXN1 and NRXN3 immunoreactivity was generally strongest in the cortical plate and increased in the ventricular zone with age, but was weak in the synaptogenic presubplate (pSP) and marginal zone. On the other hand, NRXN2 colocalized with synaptophysin in neurites of the pSP, but especially with GAP43 and CASK in growing axons of the intermediate zone. Alternative splicing modifies the role of NRXNs and we found evidence by RNAseq for exon skipping at splice site 4 and concomitant expression of KHDBRS proteins which control this splicing. NRXN2 may play a part in early cortical synaptogenesis, but NRXNs could have diverse roles in development including axon guidance, and intercellular communication between proliferating cells and/or migrating neurons.
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.|Present address: School of Healthcare Science, Manchester Metropolitan University, Manchester, M1 5GD, UK.
authors.forename: Lauren F
authors.initials: LF
authors.lastname: Harkin
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Lindsay
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.|Present address: Wellcome Trust, Sanger Institute, Cambridge, CB10 1SA, UK.
authors.forename: Yaobo
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Ayman
authors.initials: A
authors.lastname: Alzu'bi
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ferrara
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Gullon
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.|Institute of Genetic Medicine, Newcastle University, International Centre for Life, Parkway Drive, Newcastle upon Tyne NE1 3BZ, UK.|Present address: MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, EH16 4UU, UK.
authors.forename: Owen G
authors.initials: OG
authors.lastname: James
authors.affiliation: Institute of Neuroscience, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Clowry
mesh_terms: D000375:Aging / Q000378:metabolism; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D002540:Cerebral Cortex / Q000196:embryology* / Q000378:metabolism*; D047108:Embryonic Development / Q000502:physiology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007223:Infant; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019006:Neural Cell Adhesion Molecules; D055495:Neurogenesis / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; C000625937:NRXN2 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C082354:neurexin IIIalpha
keywords: cortical development; neurexins; neurodevelopmental disorders; subplate