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齿状颗粒祖细胞上皮-间充质转化转录调节因子的分化阶段特异性表达。

Differentiation stage-specific expression of transcriptional regulators for epithelial mesenchymal transition in dentate granule progenitors.

作者信息

Ohyama Kyoji, Shinohara Hiroshi M, Takayama Natsumi, Ogawa Rina, Omura Shoichiro, Hayashida Mio, Takahashi Tokiharu

机构信息

Department of Histology and Neuroanatomy, Tokyo Medical University, Tokyo, Japan.

出版信息

Front Neurosci. 2024 Aug 29;18:1425849. doi: 10.3389/fnins.2024.1425849. eCollection 2024.

DOI:10.3389/fnins.2024.1425849
PMID:39268037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11390541/
Abstract

During the development of the mouse dentate gyrus (DG), granule neuronal progenitors (GNPs) arise from glial fibrillary acidic protein (GFAP)-expressing neural stem cells in the dentate notch. However, the transcriptional regulators that control their stepwise differentiation remain poorly defined. Since neurogenesis involves epithelial-to-mesenchymal transition (EMT)-like processes, we investigated the spatio-temporal expression profiles of the EMT transcription factors Zeb1, Scratch2 (Scrt2) and Nkx6-2 in relation to known GNP markers. Our results show that Zeb1 and Scrt2 exhibit sequential, but partially overlapping expression across embryonic and postnatal stages of GNP differentiation. Zeb1 is highly enriched in -GFP+/Sox2+ neural stem/progenitor pools and subsets of Tbr2+/Prox1+/NeuroD+ intermediate GNPs, whereas Scrt2 predominates in Tbr2+/Prox1+/NeuroD+ GNPs. Strikingly, the neuronal EMT regulator Nkx6-2 shows selective expression in postnatal Tbr2+/Prox1+ GNPs, but it is excluded from embryonic counterparts. This temporally coordinated yet distinct expression of Zeb1, Scrt2 and Nkx6-2 reveals discrete transcriptional programs orchestrating GNP differentiation and neurogenic progression at embryonic versus postnatal stages of DG neurogenesis.

摘要

在小鼠齿状回（DG）发育过程中，颗粒神经元前体细胞（GNPs）起源于齿状切迹中表达胶质纤维酸性蛋白（GFAP）的神经干细胞。然而，控制其逐步分化的转录调节因子仍不清楚。由于神经发生涉及上皮-间充质转化（EMT）样过程，我们研究了EMT转录因子Zeb1、Scratch2（Scrt2）和Nkx6-2与已知GNP标志物相关的时空表达谱。我们的结果表明，Zeb1和Scrt2在GNP分化的胚胎期和出生后阶段表现出连续但部分重叠的表达。Zeb1在-GFP+/Sox2+神经干细胞/前体细胞群以及Tbr2+/Prox1+/NeuroD+中间GNPs亚群中高度富集，而Scrt2在Tbr2+/Prox1+/NeuroD+ GNPs中占主导。引人注目的是，神经元EMT调节因子Nkx6-2在出生后的Tbr2+/Prox1+ GNPs中选择性表达，但在胚胎对应物中不存在。Zeb1、Scrt2和Nkx6-2这种时间上协调但不同的表达揭示了在DG神经发生的胚胎期和出生后阶段协调GNP分化和神经发生进程的离散转录程序。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a11d/11390541/9fd04e25c469/fnins-18-1425849-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a11d/11390541/7b1cebe2246d/fnins-18-1425849-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a11d/11390541/9fd04e25c469/fnins-18-1425849-g010.jpg

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