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抑制 TrkB 和 TrkC 信号通路对食蟹猴发育新皮层神经发生的影响。

Inhibition of TrkB- and TrkC-Signaling Pathways Affects Neurogenesis in the Opossum Developing Neocortex.

机构信息

Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.

Faculty of Biology and Environmental Sciences, Cardinal Stefan Wyszynski University in Warsaw, Poland.

出版信息

Cereb Cortex. 2019 Aug 14;29(9):3666-3675. doi: 10.1093/cercor/bhy246.

DOI:10.1093/cercor/bhy246
PMID:30272136
Abstract

We have previously reported that the blockage of TrkB and TrkC signaling in primary culture of opossum neocortical cells affects neurogenesis that involves a range of processes including cell proliferation, differentiation, and survival. Here, we studied whether TrkB and TrkC activity specifically affects various types of progenitor cell populations during neocortex formation in the Monodelphis opossum in vivo. We found that the inhibition of TrkB and TrkC activities affects the same proliferative cellular phenotype, but TrkC causes more pronounced changes in the rate of cell divisions. Additionally, inhibition of TrkB and TrkC does not affect apoptosis in vivo, which was found in cell culture experiments. The lack of TrkB and TrkC receptor activity caused the arrest of newly generated neurons; therefore, they could not penetrate the subplate zone. We suggest that at this time point in development, migration consists of 2 steps. During the initial step, neurons migrate and reach the base of the subplate, whereas during the next step the migration of neurons to their final position is regulated by TrkB or TrkC signaling.

摘要

我们之前曾报道过,阻断负鼠新皮质细胞原代培养中的 TrkB 和 TrkC 信号会影响神经发生,涉及包括细胞增殖、分化和存活在内的一系列过程。在这里,我们研究了在体内,TrkB 和 TrkC 的活性是否会特异性地影响 Monodelphis opossum 新皮质形成过程中的各种祖细胞群体。我们发现,抑制 TrkB 和 TrkC 的活性会影响相同的增殖细胞表型,但 TrkC 会导致细胞分裂率发生更明显的变化。此外,抑制 TrkB 和 TrkC 并不影响细胞培养实验中观察到的体内细胞凋亡。缺乏 TrkB 和 TrkC 受体活性会导致新生成的神经元停滞,因此它们无法穿透基板层。我们认为,在发育的这个时间点,迁移由两个步骤组成。在初始步骤中,神经元迁移并到达基板层的底部,而在下一个步骤中,神经元向其最终位置的迁移受 TrkB 或 TrkC 信号的调节。

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