一个由BMP控制的代谢/表观遗传信号级联指导面部中部形态发生
Jingwen Yang1,2, Lingxin Zhu1,3, Haichun Pan2
1State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China.
The Journal of clinical investigation
|March 11, 2024
概括
骨形态遗传蛋白 (BMP) 信号调节面发育,通过控制神经细胞 (CNCC) 中的乳酸盐生产和基因素乳化. 这种代谢-表观遗传轴对于预防中线面部缺陷至关重要.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 代谢调节 代谢调节 代谢调节
背景情况:
- 面异常,特别是中线缺陷,是常见的出生缺陷,对健康有重大影响.
- 在面形态发生过程中,遗传,信号和代谢途径的协调还没有完全被理解.
研究的目的:
- 研究骨形态遗传蛋白 (BMP) 信号传导在面发育中的作用.
- 阐明神经细胞 (CNCCs) 中BMP信号传导,代谢和表观遗传学之间的机制.
主要方法:
- 利用构成性激活的ACVR1 (ca-ACVR1) 来操纵CNCC中的BMP信号.
- 评估了糖分的活性,乳酸盐的产生,以及组织蛋白的乳酸化.
- 分析了基因表达的变化,包括Pdgfra,在体外和体内.
主要成果:
- 升高的BMP信号通过p53依赖的途径抑制了糖解和乳酸生产,导致严重的中线面部缺陷.
- 依赖BMP信号的乳酸生成促进了基因素乳化,改变了Pdgfra基因表达,调节了CNCC的行为.
- 建立了BMP信号,代谢活动和面发育中的表观遗传修饰之间的联系.
结论:
- BMP信号编排了一种代谢和表观遗传级联,涉及乳酸生产和基因素乳化,这对于面形态发生是必不可少的.
- 这个轴的调节失调会导致先天性面出生缺陷.
- 调节代谢驱动的组分激素乳化为这些缺陷提供了潜在的预防策略.
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