Alhesain Maznah, Ronan Hannah, LeBeau Fiona E N, Clowry Gavin J
Centre for Transformative Research in Neuroscience, Newcastle University Biosciences Institute, Newcastle upon Tyne, United Kingdom.
Front Neurosci. 2023 Sep 8;17:1249973. doi: 10.3389/fnins.2023.1249973. eCollection 2023.
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 as being directly, or indirectly, implicated in schizophrenia susceptibility. To explore potential roles in normal early human forebrain neurodevelopment, we mapped expression by region and cell type.
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 hybridization and immunohistochemistry against mRNA and protein, and other marker proteins.
Tissue RNAseq revealed that 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, was highly expressed in progenitor zones at early developmental stages, showing lower expression in post-mitotic cells.
FEZ1 has different expression patterns and potentially diverse functions in discrete forebrain regions during prenatal human development.
成束和延伸蛋白ζ-1（FEZ1）参与轴突生长，但可能与多种蛋白质相互作用，其作用范围从细胞内运输到转录调控。基因关联研究和其他研究已确定其直接或间接与精神分裂症易感性有关。为了探索其在正常人类早期前脑神经发育中的潜在作用，我们按区域和细胞类型绘制了FEZ1的表达图谱。
所有组织均获得母亲的同意，并经人类发育生物学资源中心的伦理批准。RNA测序数据来自先前发表的资料。取自受孕后8至21周（PCW）样本的薄石蜡切片用于RNAscope杂交以及针对FEZ1 mRNA和蛋白质以及其他标记蛋白的免疫组织化学检测。
组织RNA测序显示，FEZ1在受孕后7.5至17周的人类大脑皮层中高度表达，而在受孕后17至18周的单细胞RNA测序证实其在所有神经外胚层来源的细胞中均有表达。在更成熟的谷氨酸能神经元中表达水平最高，在GABA能神经元和分裂中的祖细胞中最低。在丘脑中，单细胞RNA测序同样证实其在多种细胞类型中表达。在受孕后8至10周的大脑皮层切片中，mRNA和蛋白质的强表达似乎局限于有丝分裂后的神经元，在祖细胞区表达较低。到受孕后16至19周时，在一些轴突束中观察到蛋白质表达。然而，在皮层下区域，FEZ1在发育早期的祖细胞区高度表达，在有丝分裂后的细胞中表达较低。
在人类产前发育过程中，FEZ1在离散的前脑区域具有不同的表达模式和潜在的多种功能。
