在远端脏片段的构成性Yap激活破坏了上皮质的身份和脏模式
Zeinab Dehghani-Ghobadi1,2, Eunah Chung1,2, Mohammed Sayed3
1Feinberg Cardiovascular & Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
bioRxiv : the preprint server for biology
|December 22, 2025
概括
在脏的远端卷状管 (DCT) 和连接管 (CNT) 中持续的Yap激活会破坏细胞的身份和结构. 这种信号也会影响邻近的近接管的发育,突出显示Hippo-Yap通路在的恒常性中的作用.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 远端卷状管 (DCT) 和连接管 (CNT) 对于电解质平衡和平衡至关重要.
- 河马通路在脏发育中的作用已知,但其在远端脏片段中的功能尚不清楚.
研究的目的:
- 为了研究Yap的功能,一个河马通路效应器,在远端脏片段.
- 了解Yap功能增益对上皮组织和脏细分的影响.
主要方法:
- 产生了一个Cre诱导的Yap功能增益等位基因 (Col1a1-Yap5SA).
- 为了Yap激活,使用了特定于远端脏的Slc12a3Cre驱动器.
- 进行了表型,分子和转录组分析.
主要成果:
- Slc12a3Cre针对DCT和CNT,表明CNT可能来自DCT细胞.
- 构成性Yap激活导致了增强的增殖,细胞迁移和上皮细胞到介质细胞的过渡.
- 观察到受损的DCT/CNT标记表达,极性和结点架构.
- 突变脏显示近接管标志物下调,表明非细胞自主效应.
结论:
- 在远端脏片段中持续的Yap激活会破坏表皮质的完整性和身份.
- 雅普激活对脏模式产生非细胞自主作用,影响近端管道.
- 严格调节Hippo-Yap信号传递对于维持脏上皮质结构和脏细分至关重要.
相关概念视频
Nephrons
6.2K
The kidneys are intricate organs with millions of working units known as nephrons. Each nephron features two major structures: the renal corpuscle, which facilitates blood plasma filtration, and the renal tubule, which handles the glomerular filtrate. Blood supply is directly linked to the nephrons. The renal corpuscle consists of the glomerulus, a capillary network, and the Bowman's capsule, a double-walled epithelial structure that encases the glomerulus. The filtering of blood plasma...
6.2K
Renal Tubule and Collecting Duct
3.0K
The renal tubule is divided into three parts: the proximal convoluted tubule (PCT), the Loop of Henle (LOH), and the distal convoluted tubule (DCT).
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
3.0K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.4K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.4K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.6K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.6K
Cadherins in Tissue Organization
3.8K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.8K
Notch Signaling Pathway
6.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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...
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...
6.3K


