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Notch信号通路塑造神经外胚层,并调节海胆胚胎中神经祖细胞的不对称分裂。

Notch signaling patterns neurogenic ectoderm and regulates the asymmetric division of neural progenitors in sea urchin embryos.

作者信息

Mellott Dan O, Thisdelle Jordan, Burke Robert D

机构信息

Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada V8W 2Y2.

Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada V8W 2Y2

出版信息

Development. 2017 Oct 1;144(19):3602-3611. doi: 10.1242/dev.151720. Epub 2017 Aug 29.

Abstract

We have examined regulation of neurogenesis by Delta/Notch signaling in sea urchin embryos. At gastrulation, neural progenitors enter S phase coincident with expression of Sp-SoxC. We used a BAC containing knocked into the locus to label neural progenitors. Live imaging and immunolocalizations indicate that Sp-SoxC-expressing cells divide to produce pairs of adjacent cells expressing GFP. Over an interval of about 6 h, one cell fragments, undergoes apoptosis and expresses high levels of activated Caspase3. A Notch reporter indicates that Notch signaling is activated in cells adjacent to cells expressing Sp-SoxC. Inhibition of γ-secretase, injection of Sp-Delta morpholinos or CRISPR/Cas9-induced mutation of results in supernumerary neural progenitors and neurons. Interfering with Notch signaling increases neural progenitor recruitment and pairs of neural progenitors. Thus, Notch signaling restricts the number of neural progenitors recruited and regulates the fate of progeny of the asymmetric division. We propose a model in which localized signaling converts ectodermal and ciliary band cells to neural progenitors that divide asymmetrically to produce a neural precursor and an apoptotic cell.

摘要

我们研究了海胆胚胎中Delta/Notch信号通路对神经发生的调控。在原肠胚形成期,神经祖细胞进入S期,同时Sp-SoxC表达。我们使用一个含有敲入基因座的BAC来标记神经祖细胞。实时成像和免疫定位表明,表达Sp-SoxC的细胞分裂产生表达GFP的相邻细胞对。在大约6小时的时间间隔内,一个细胞破碎,发生凋亡并表达高水平的活化Caspase3。一个Notch报告基因表明,Notch信号通路在与表达Sp-SoxC的细胞相邻的细胞中被激活。γ-分泌酶的抑制、Sp-Delta吗啉代寡核苷酸的注射或CRISPR/Cas9诱导的基因座突变导致神经祖细胞和神经元数量过多。干扰Notch信号通路会增加神经祖细胞的招募和神经祖细胞对的数量。因此,Notch信号通路限制了招募的神经祖细胞数量,并调节不对称分裂后代的命运。我们提出了一个模型,其中局部信号将外胚层细胞和纤毛带细胞转化为神经祖细胞,这些神经祖细胞进行不对称分裂,产生一个神经前体和一个凋亡细胞。

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