Alteration of the Retinoid Acid-CBP Signaling Pathway in Neural Crest Induction Contributes to Enteric Nervous System Disorder
Alteration of the Retinoid Acid-CBP Signaling Pathway in Neural Crest Induction Contributes to Enteric Nervous System Disorder
复制标题
神经嵴诱导过程中视黄酸-CBP 信号通路的改变导致肠神经系统紊乱。
DOI：
10.3389/fped.2018.00382
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发表时间：
2018-12
影响因子：
2.6
通讯作者：
Tingyu Li
中科院分区：
文献类型：
--
作者：
Cheng Li;Rong Hu;Nali Hou;Yi Wang;Zhili Wang;Ting Yang;Yan Gu;Mulan He;Yu Shi;Jie Chen;Weihong Song;Tingyu Li
先天性巨结肠病（HSCR）和/或神经节减少症是由肠神经嵴细胞（ENCCs）发育缺陷引起的常见儿科疾病。维甲酸（RA）信号传导已被证明影响神经嵴（NC）的发育。然而，RA缺陷引起的HSCR或神经节过少症的机制尚不明确。在本报告中，我们发现在HSCR患者肠道中，RA核受体RARα及其相互作用的协同调节因子creb结合蛋白（CBP）在正常神经节段的肠神经丛中表达。然而，这两个基因在病理性神经节段的表达明显受到抑制。在非洲爪蟾（Xenopus laevis）动物模型中，内源性RARα与CBP相互作用并在NC领地表达。morolino介导的RARα下调可阻断NC标记基因Sox10和FoxD3的表达，抑制NC诱导。变形胚胎表现出胃肠道神经细胞减少，这是一种典型的肠道神经缺陷相关表型。注射CBP mRNA恢复NC诱导并减少肠神经缺陷相关表型。我们的研究表明，RARα在NC诱导过程中通过CBP调控Sox10的表达，而RA-CBP信号通路的改变可能与肠神经系统疾病的发生有关。
Hirschsprung Disease (HSCR) and/or hypoganglionosis are common pediatric disorders that arise from developmental deficiencies of enteric neural crest cells (ENCCs). Retinoid acid (RA) signaling has been shown to affect neural crest (NC) development. However, the mechanisms underlying RA deficiency-induced HSCR or hypoganglionosis are not well-defined. In this report, we found that in HSCR patient bowels, the RA nuclear receptor RARα and its interacting coregulator CREB-binding protein (CBP) were expressed in enteric neural plexuses in the normal ganglionic segment. However, the expression of these two genes was significantly inhibited in the pathological aganglionic segment. In a Xenopus laevis animal model, endogenous RARα interacted with CBP and was expressed in NC territory. Morpholino-mediated knockdown of RARα blocked expression of the NC marker genes Sox10 and FoxD3 and inhibited NC induction. The morphant embryos exhibited reduced nervous cells in the gastrointestinal anlage, a typical enteric nervous deficiency-associated phenotype. Injection of CBP mRNA rescued NC induction and reduced enteric nervous deficiency-associated phenotypes. Our work demonstrates that RARα regulates Sox10 expression via CBP during NC induction, and alteration of the RA-CBP signaling pathway may contribute to the development of enteric nervous system disorders.
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DOI：
10.1097/mpg.0b013e3182a934c7
发表时间：
2013-12
影响因子：
2.9
作者：
Andrea Volpe;R. Alaggio;P. Midrio;L. Iaria;P. Gamba
通讯作者：
Andrea Volpe;R. Alaggio;P. Midrio;L. Iaria;P. Gamba
CBP 和 p300 对 RA 介导的小鼠胚胎干细胞减数分裂基因 Stra8 表达的不同作用
影响因子：
3.7
作者：
Chen W;Jia W;Wang K;Si X;Zhu S;Duan T;Kang J
通讯作者：
Kang J
影响因子：
3.7
作者：
Simkin JE;Zhang D;Rollo BN;Newgreen DF
通讯作者：
Newgreen DF
影响因子：
16.2
作者：
Lee, Seunghee;Lee, Bora;Lee, Jae W.;Lee, Soo-Kyung
通讯作者：
Lee, Soo-Kyung
影响因子：
5.1
作者：
Hou, Nali;Ren, Lan;Li, Tingyu
通讯作者：
Li, Tingyu