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赖氨酸去甲基酶 3a 在非洲爪蟾胚胎发生中的颅面和神经发育中的作用。

Lysine demethylase 3a in craniofacial and neural development during Xenopus embryogenesis.

机构信息

Cell and Matrix Research Institute, Kyungpook National University‑Center for Nonlinear Dynamics, School of Life Sciences, Brain Korea 21 Plus Kyungpook National University Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.

School of Life Sciences, Ulsan National Institute of Science and Technology, Ulsan 44919, Republic of Korea.

出版信息

Int J Mol Med. 2019 Feb;43(2):1105-1113. doi: 10.3892/ijmm.2018.4024. Epub 2018 Dec 11.

Abstract

Epigenetic modifier lysine demethylase 3a (Kdm3a) specifically demethylates mono‑ and di‑methylated ninth lysine of histone 3 and belongs to the Jumonji domain‑containing group of demethylases. Kdm3a serves roles during various biological and pathophysiological processes, including spermatogenesis and metabolism, determination of sex, androgen receptor‑mediated transcription and embryonic carcinoma cell differentiation. In the present study, physiological functions of Kdm3a were evaluated during embryogenesis of Xenopus laevis. Spatiotemporal expression pattern indicated that kdm3a exhibited its expression from early embryonic stages until tadpole stage, however considerable increase of kdm3a expression was observed during the neurula stage of Xenopus development. Depleting kdm3a using kdm3a antisense morpholino oligonucleotides induced anomalies, including head deformities, small‑sized eyes and abnormal pigmentation. Whole‑mount in situ hybridization results demonstrated that kdm3a knockdown was associated with defects in neural crest migration. Further, quantitative polymerase chain reaction revealed abnormal expression of neural markers in kdm3a morphants. RNA sequencing of kdm3a morphants indicated that kdm3a was implicated in mesoderm formation, cell adhesion and metabolic processes of embryonic development. In conclusion, the results of the present study indicated that Kdm3a may serve a role in neural development during Xenopus embryogenesis and may be targeted for treatment of developmental disorders. Further investigation is required to elucidate the molecular mechanism underlying the regulation of neural development by Kdm3a.

摘要

表观遗传修饰赖氨酸去甲基酶 3a(Kdm3a)特异性地去除组蛋白 3 的单甲基和二甲基第 9 位赖氨酸,属于包含 Jumonji 结构域的去甲基酶组。Kdm3a 在各种生物学和病理生理学过程中发挥作用,包括精子发生和代谢、性别决定、雄激素受体介导的转录和胚胎癌细胞分化。在本研究中,评估了 Kdm3a 在非洲爪蟾(Xenopus laevis)胚胎发生过程中的生理功能。时空表达模式表明,kdm3a 从早期胚胎阶段表达到蝌蚪阶段,但在非洲爪蟾发育的神经胚阶段观察到 kdm3a 表达的显著增加。使用 kdm3a 反义吗啉代寡核苷酸耗尽 kdm3a 会诱导异常,包括头部畸形、眼睛小和色素异常。整体原位杂交结果表明,kdm3a 敲低与神经嵴迁移缺陷有关。此外,定量聚合酶链反应显示 kdm3a 突变体中神经标记物的异常表达。kdm3a 突变体的 RNA 测序表明,kdm3a 参与中胚层形成、细胞黏附和胚胎发育的代谢过程。综上所述,本研究结果表明,Kdm3a 可能在非洲爪蟾胚胎发生过程中的神经发育中发挥作用,并且可能成为治疗发育障碍的靶点。需要进一步研究阐明 Kdm3a 调节神经发育的分子机制。

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