与口腔面部裂相关的E-cadherin变体以依赖REG1A的方式触发异常细胞运动
Joana Pereira1,2,3, Soraia Melo1,2, Rui M Ferreira1,2
1i3S - Instituto de Investigação e Inovação em Saúde, Universidade Do Porto, Rua Alfredo Allen, 208, Porto, 4200-135, Portugal.
与口腔面部裂 (OFC) 相关的E-cadherin突变导致过度的细胞迁移和适应微环境. 这项研究揭示了OFC变体如何改变细胞行为,影响组织发育.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
背景情况:
- 在E-cadherin的生殖基因突变与遗传性扩散性胃癌 (HDGC) 和先天性形,如口腔面部裂 (OFC) 相关.
- 关联E-cadherin功能丧失与OFC等不同的临床结果的确切分子机制尚不清楚.
- 由E-cadherin功能障碍引起的障碍被假设涉及异常的细胞外矩阵相互作用和细胞内信号,破坏细胞迁移协调.
研究的目的:
- 调查与E-cadherin相关的口腔面部裂 (OFC) 相比遗传扩散胃癌 (HDGC) 背后的独特分子机制.
- 模拟和分析特定E-cadherin变体对细胞形态和细胞迁移 in vitro 和 in vivo 的影响.
- 确定导致OFC中观察到的异常细胞运动的遗传和分子因素.
主要方法:
- 对OFC和HDGC相关的E-cadherin突变体进行体内和体外模型的开发.
- 利用Drosophila模型来评估E-cadherin变体对细胞形态和迁移的影响.
- 采用差距关闭测定,时隔显微镜,高通量ECM阵列和RNA测序来分析细胞迁移,粘附和转录组形状.
主要成果:
- 具有OFC相关的E-cadherin变体的细胞表现出高运动性和不规则的前缘,损害了协调的上皮细胞运动.
- 与HDGC变体相比,OFC变体增加了细胞对多种细胞外基质的粘附,表明微环境可塑性得到了增强.
- RNA测序确定了OFC细胞中的独特的转录组形状,突出了REG1A作为潜在的调节者;它的抑制使迁移模式正常化.
结论:
- 与OFC相关的E-cadherin变体激活信号通路,促进细胞适应性和动态重组.
- 这种增强的细胞可塑性有助于异常的组织成型和运动,可能解释口腔面部形的病因.
- 这些发现阐明了特定的E-cadherin突变如何通过改变细胞矩阵相互作用和信号传递导致不同的发育结果.
更多相关视频
07:26Isolation of Whole Cell Protein Lysates from Mouse Facial Processes and Cultured Palatal Mesenchyme Cells for Phosphoprotein Analysis
Published on: April 1, 2022
07:13Isolation and Time-Lapse Imaging of Primary Mouse Embryonic Palatal Mesenchyme Cells to Analyze Collective Movement Attributes
Published on: February 13, 2021
相关概念视频
Cadherins in Tissue Organization
Cell Sorting During Development
Cell sorting plays an...
Structure of Cadherins
Catenins
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Intracellular Signaling Affects Focal Adhesions
Some...
Cytoskeletal Coordination in Cell Migration
Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
