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异染色质蛋白 1β通过抑制非洲爪蟾多能性相关基因 pou5f3.2/oct25 来调节神经和神经嵴发育。

Heterochromatin protein 1 beta regulates neural and neural crest development by repressing pluripotency-associated gene pou5f3.2/oct25 in Xenopus.

机构信息

Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

出版信息

Dev Dyn. 2021 Aug;250(8):1113-1124. doi: 10.1002/dvdy.319. Epub 2021 Feb 26.

Abstract

BACKGROUND

Heterochromatin protein 1 (HP1) is associated with and plays a role in compact chromatin conformation, but the function of HP1 in vertebrate embryogenesis is not understood completely.

RESULTS

Here, we explore the activity of HP1 in early neural development in the frog Xenopus laevis. We show that the three isoforms of HP1, HP1α, β, and γ, are expressed in similar patterns in the neural and neural crest derivatives in early embryos. Despite this, knockdown of HP1β and HP1γ, but not HP1α, in presumptive neural tissues leads to head defects. Late pan-neural markers and neural crest specifier genes are reduced, but early neural and neural plate border genes are less affected in the morphant embryos. Further investigation reveals that neuronal differentiation is impaired and a pluripotency-associated gene, pou5f3.2/oct25, is expanded in HP1β morphants. Ectopic expression of pou5f3.2/oct25 mimics the effect of HP1β knockdown on marker expression, whereas simultaneous knockdown of HP1β and pou5f3.2/oct25 partially rescues expression of these genes.

CONCLUSION

Taken together, the data suggest that HP1β regulates transition from precursor to more differentiated cell types during neural and neural crest development in Xenopus, and it does so at least partially via repression of the pluripotency-associated transcription regulator pou5f3.2/oct25.

摘要

背景

异染色质蛋白 1(HP1)与致密染色质构象相关,并在其中发挥作用,但它在脊椎动物胚胎发生中的功能尚未完全了解。

结果

在这里,我们探索了青蛙 Xenopus laevis 早期神经发育过程中 HP1 的活性。我们表明,HP1 的三种同工型,HP1α、β 和 γ,在早期胚胎的神经和神经嵴衍生物中以相似的模式表达。尽管如此,在假定的神经组织中敲低 HP1β 和 HP1γ,但不是 HP1α,会导致头部缺陷。晚期全神经标记物和神经嵴特化基因减少,但形态发生胚胎中的早期神经和神经板边界基因受影响较小。进一步的研究表明,神经元分化受损,多能相关基因 pou5f3.2/oct25 在 HP1β 形态发生体中扩增。pou5f3.2/oct25 的异位表达模拟了 HP1β 敲低对标记物表达的影响,而同时敲低 HP1β 和 pou5f3.2/oct25 则部分挽救了这些基因的表达。

结论

综上所述,数据表明 HP1β 在 Xenopus 的神经和神经嵴发育过程中调节从前体细胞向更分化的细胞类型的转变,至少部分通过抑制多能相关转录调节因子 pou5f3.2/oct25 来实现。

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