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Expression of the schizophrenia associated gene FEZ1 in the early developing fetal human forebrain

Lookup NU author(s): Maznah Alhesain, Hannah Ronan, Dr Fiona LeBeauORCiD, Dr Gavin ClowryORCiD

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


Abstract

Copyright © 2023 Alhesain, Ronan, LeBeau and Clowry. Introduction: The protein fasciculation and elongation zeta-1 (FEZ1) is involved in axon outgrowth but potentially interacts with various proteins with roles ranging from intracellular transport to transcription regulation. Gene association and other studies have identified FEZ1 as being directly, or indirectly, implicated in schizophrenia susceptibility. To explore potential roles in normal early human forebrain neurodevelopment, we mapped FEZ1 expression by region and cell type. Methods: All tissues were provided with maternal consent and ethical approval by the Human Developmental Biology Resource. RNAseq data were obtained from previously published sources. Thin paraffin sections from 8 to 21 post-conceptional weeks (PCW) samples were used for RNAScope in situ hybridization and immunohistochemistry against FEZ1 mRNA and protein, and other marker proteins. Results: Tissue RNAseq revealed that FEZ1 is highly expressed in the human cerebral cortex between 7.5–17 PCW and single cell RNAseq at 17–18 PCW confirmed its expression in all neuroectoderm derived cells. The highest levels were found in more mature glutamatergic neurons, the lowest in GABAergic neurons and dividing progenitors. In the thalamus, single cell RNAseq similarly confirmed expression in multiple cell types. In cerebral cortex sections at 8–10 PCW, strong expression of mRNA and protein appeared confined to post-mitotic neurons, with low expression seen in progenitor zones. Protein expression was observed in some axon tracts by 16–19 PCW. However, in sub-cortical regions, FEZ1 was highly expressed in progenitor zones at early developmental stages, showing lower expression in post-mitotic cells. Discussion: FEZ1 has different expression patterns and potentially diverse functions in discrete forebrain regions during prenatal human development.


Publication metadata

Author(s): Alhesain M, Ronan H, LeBeau FEN, Clowry GJ

Publication type: Article

Publication status: Published

Journal: Frontiers in Neuroscience

Year: 2023

Volume: 17

Online publication date: 08/09/2023

Acceptance date: 15/08/2023

Date deposited: 03/10/2023

ISSN (print): 1662-4548

ISSN (electronic): 1662-453X

Publisher: Frontiers Media SA

URL: https://doi.org/10.3389/fnins.2023.1249973

DOI: 10.3389/fnins.2023.1249973

Data Access Statement: The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: https://www.ebi.ac.uk/metagenomics/, E-MTAB-4840.


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Funding

Funder referenceFunder name
099175/Z/12/ZWellcome Trust
Al Qassim University, Saudi Arabia
MR/R006237/1Medical Research Council (MRC)
MC/PC/13047
MRC

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