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对面形态发生的ESCRT依赖控制,同时扰乱NOTCH信号传输

Viviana Hermosilla Aguayo¹, Peter Martin¹, Nuo Tian¹

¹Program in Craniofacial Biology, Institute for Human Genetics, Eli and Edythe Broad Center of Regeneration Medicine & Stem Cell Research, Dept of Orofacial Sciences and Dept of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.

Developmental biology

|August 12, 2023

概括

运输所需的内体组分复合体 (ESCRT) 机器,特别是Vps25,对于小鼠的面发育至关重要. 破坏Vps25导致严重的面缺陷,并影响NOTCH信号传输.

科学领域:

发展生物学发展生物学
分子生物学分子生物学
遗传学是一个遗传学.

背景情况:

面发育依赖于复杂的调节网络,包括信号通路和内溶酶体贩运.
虽然ESCRT机械对于内体体贩运和受体退化至关重要,但其在脊椎动物面发育中的作用尚未得到充分研究.
以前的研究在体外和无脊椎动物中确定了ESCRT功能,突出显示了脊椎动物发育研究中的差距.

研究的目的:

研究ESCRT-II组件Vps25在小鼠面发育中的作用.
在一个新的Vps25低形态小鼠模型中描述面异常.
探索老鼠发育过程中ESCRT编码基因的时空表达及其对信号通路的影响.

主要方法:

诱导突变发生 (ENU) 来产生一个Vps25低形态小鼠系 (Vps25^ENU/ENU).
在小鼠发育过程中评估Vps25和其他ESCRT基因表达模式.
对Vps25^ENU/ENU胚胎的表型分析,专注于面结构.
调查NOTCH信号通路活动在受影响的面领域.

主要成果:

Vps25和其他ESCRT基因在无处不在地表达,在面,心脏和四肢领域的丰富.
Vps25^ENU/ENU胚胎表现出晚期致死性和显著的头骨面部缺陷,包括下缺血,鼻子缩短,耳朵形和口腔裂.
在Vps25^ENU/ENU胚胎的面区域观察到NOTCH信号的扰乱.

结论:

这项研究为ESCRT-II在脊椎动物面形态发生过程中的关键作用提供了第一个证据.
Vps25^ENU/ENU小鼠模型重复了人类先天性面综合征的特征.
NOTCH信号通路的失调与Vps25^ENU/ENU胚胎中观察到的面缺陷有关,这表明一种保存的发育机制.

关键词:

头骨面部头骨面部面部这是ESCRT的特点.下下的下是什么意思鼠标鼠标是一个鼠标.在NOTCH信号中发出信号.在 Vps2525 中使用.

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