FoxG1 Directly Represses Dentate Granule Cell Fate During Forebrain Development
FoxG1 Directly Represses Dentate Granule Cell Fate During Forebrain Development
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FoxG1 在前脑发育过程中直接抑制齿状颗粒细胞的命运
DOI：
10.3389/fncel.2018.00452
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发表时间：
2018-11-23
影响因子：
5.3
通讯作者：
Zhao, Chunjie
中科院分区：
文献类型：
--
作者：
Han, Xiao;Gu, Xiaochun;Zhao, Chunjie
皮质由数百个神经元亚型组成，这些神经元亚型被组织成不同的功能区域；然而，细胞命运决定的机制仍不清楚。 Foxg1 参与多种发育过程，包括端脑模式、细胞增殖和细胞命运决定。 Foxg1 的组成性破坏导致皮质神经元转化为 Cajal-Retzius (CR) 细胞，同时通过消耗皮质而导致皮质下摆大幅扩张。然而，另一组报告称，发育中的端脑的外侧到内侧的重新模式大，而不是诱导细胞命运转换，作为细胞类型输出变化的解释。在这里，我们通过将 Foxg1(fl/fl) 小鼠与 Nestin-CreER (TM) 小鼠杂交，并在 E10.5 开始的不同发育阶段结合他莫昔芬 (TM) 诱导，有条件地破坏端脑祖细胞中的 Foxg1，以进一步阐明 FoxG1 在端脑模式形成后细胞命运决定中的作用。皮质中齿状回（DG）颗粒样细胞的数量显着增加。甚至在 E14.5 删除后也检测到了这种增加。体内镶嵌缺失和体外细胞培养进一步揭示了 FoxG1 在抑制颗粒细胞命运中的细胞自主作用。然而，海马体形成和发育所需的皮质边缘仅略微增大，因此可能对细胞命运转换没有贡献。 Lef1 的表达在侧皮质 VZ 中显着上调，而 FoxG1 可能在 Wnt 信号传导的上游发挥作用。我们的结果为 FoxG1 的功能和端脑发育过程中细胞命运决定的机制提供了新的见解。
The cortex consists of 100s of neuronal subtypes that are organized into distinct functional regions; however, the mechanisms underlying cell fate determination remain unclear. Foxg1 is involved in several developmental processes, including telencephalic patterning, cell proliferation and cell fate determination. Constitutive disruption of Foxg1 leads to the transformation of cortical neurons into Cajal-Retzius (CR) cells, accompanied by a substantial expansion of the cortical hem through the consumption of the cortex. However, rather than the induction of a cell fate switch, another group has reported a large lateral to medial repatterning of the developing telencephalon as the explanation for this change in cell type output. Here, we conditionally disrupted Foxg1 in telencephalic progenitor cells by crossing Foxg1(fl/fl) mice with Nestin-CreER (TM) mice combined with tamoxifen (TM) induction at distinct developmental stages beginning at E10.5 to further elucidate the role of FoxG1 in cell fate determination after telencephalon pattern formation. The number of dentate gyrus (DG) granule-like cells was significantly increased in the cortex. The increase was even detected after deletion at E14.5. In vivo mosaic deletion and in vitro cell culture further revealed a cell-autonomous role for FoxG1 in repressing granule cell fate. However, the cortical hem, which is required for the patterning and the development of the hippocampus, was only slightly enlarged and thus may not contribute to the cell fate switch. Lef1 expression was significantly upregulated in the lateral, cortical VZ and FoxG1 may function upstream of Wnt signaling. Our results provide new insights into the functions of FoxG1 and the mechanisms of cell fate determination during telencephalic development.