卡德林粘附复合体在Wnt诱导的脏前代细胞的上皮过渡中直接细胞聚合
Balint Der1,2,3, Helena Bugacov1,4, Bohdana-Myroslava Briantseva1
1Department of Stem Cell Biology and Regenerative Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA.
概括
在发育过程中,β-catenin (Ctnnb1) 将Wnt信号与细胞聚合联系起来. 这一过程对生至关重要,涉及素介导的细胞粘附,对于原细胞中介细胞转移至关重要.
科学领域:
- 发展生物学 发展生物学
- 细胞生物学 细胞生物学
- 脏生理学 脏生理学
背景情况:
- 哺乳动物脏发育中的脏形成是由脏原生细胞 (NPC) 发起的.
- 在NPC中,Wnt信号激活了β-catenin (Ctnnb1) 驱动的转录程序和介质细胞到上皮细胞的转换 (MET).
研究的目的:
- 调查β-catenin在发育过程中的NPC聚合和MET中的作用.
- 阐明Wnt诱导的NPC聚合背后的分子机制及其对细胞粘附分子的依赖.
主要方法:
- 利用一个实验室老鼠NPC培养模型.
- 使用基因操纵 (基因去除) 来评估β-catenin,cadherins和catenin的功能.
- 调节细胞外水平以研究细胞-细胞接触动态.
- 进行了分子分析,以确定卡德林表达和β-catenin介导的转录变化.
主要成果:
- Wnt通路的激活诱导了NPC聚合,这是MET的一个关键步骤,依赖于β-catenin.
- NPC聚合是Ca2+依赖的,这意味着由素介导的细胞粘附.
- 在NPC MET期间β-catenin上调调节了卡德林3 (Cdh3) 和卡德林4 (Cdh4).
- 基因去除cadherins或破坏α-catenin相互作用取消了聚合,但没有Wnt通路的诱导.
结论:
- β-catenin 是一个关键的调解者,将Wnt驱动的转录程序与NPC形态发生联系起来.
- 由β-catenin调节的卡德林介导的细胞粘附在发育过程中对NPC聚合至关重要.
- 这些发现澄清了发生的分子基础,并提供了对发育性脏疾病的见解.
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