■蛋白质束状和伸长zeta-1(FEZ1)参与轴突生长,但可能与各种蛋白质相互作用,作用范围从细胞内运输到转录调节。基因关联和其他研究已经确定FEZ1是直接的,或者间接地,与精神分裂症易感性有关。探讨在正常早期人类前脑神经发育中的潜在作用,我们通过区域和细胞类型映射了FEZ1表达。
■所有组织均获得人类发育生物学资源的母亲同意和伦理批准。RNAseq数据从先前公布的来源获得。受孕后8至21周(PCW)样品的石蜡切片用于RNAScope原位杂交和针对FEZ1mRNA和蛋白质的免疫组织化学,和其他标记蛋白。
■组织RNAseq显示,FEZ1在7.5-17PCW之间的人类大脑皮层中高度表达,而在17-18PCW的单细胞RNAseq证实了其在所有神经外胚层来源的细胞中的表达。在更成熟的谷氨酸能神经元中发现了最高水平,在GABA能神经元和分裂祖细胞中最低。在丘脑里,单细胞RNAseq类似地证实在多种细胞类型中的表达。在8-10PCW的大脑皮层切片中,mRNA和蛋白质的强烈表达似乎局限于有丝分裂后的神经元,在祖细胞区见低表达。16-19PCW在一些轴突束中观察到蛋白质表达。然而,在皮质下区域,FEZ1在早期发育阶段在祖细胞区高表达,在有丝分裂后细胞中显示较低的表达。
■FEZ1在产前人类发育过程中的离散前脑区域具有不同的表达模式和潜在的不同功能。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: FEZ1 has different expression patterns and potentially diverse functions in discrete forebrain regions during prenatal human development.