BRD4与神经的活性增强剂结合,在骨质母细胞分化过程中调节RUNX2活性
Rachel E Musa1, Kaitlyn L Lester1, Gabrielle Quickstad1
1Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA.
概括
康尼莉亚·德朗格综合征 (CdLS) 是由BRD4突变引起的,BRD4是一种对面发育至关重要的蛋白质. 神经细胞中的BRD4损失会损害骨质母细胞的分化,导致严重的面部异常.
科学领域:
- 发展生物学 发展生物学
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
背景情况:
- 康尼利亚·德朗格综合征 (CdLS) 是一种先天性疾病,其特征是面部形,生长缺陷,认知障碍和四肢异常.
- CdLS在遗传上是异质的,BRD4突变,一种被认为是病因的原蛋白蛋白.
研究的目的:
- 通过研究小鼠神经细胞 (NCC) 在面发育过程中BRD4的作用来建模CdLS面部病理.
- 描述BRD4在面发育中的细胞和分子功能.
主要方法:
- 产生了对BRD4.4的NCC特异性功能丧失的小鼠模型.
- 分析了这些模型中面发育的细胞和分子机制.
- 研究了BRD4和RUNX2在骨质细胞分化中的相互作用.
主要成果:
- 在NCC中BRD4功能丧失导致严重的面部缺血,口腔裂,面部中间裂和小鼠脑外,受影响的新生儿在出生时死亡.
- BRD4突变的NCC启动了RUNX2表达,但未能诱导骨质细胞谱系承诺所必需的下游目标.
- 发现BRD4可以结合活性增强剂,调节骨质性转录因子和细胞外基因组件,其与RUNX2的关联对骨质细胞分化至关重要.
结论:
- BRD4在面骨发育中起着至关重要的作用.
- BRD4通过控制骨质细胞增强剂来调节RUNX2转录程序,影响骨形成.
- 破坏BRD4功能导致类似于CdLS的面部病理.
相关概念视频
Determination
18.5K
During embryogenesis, cells become progressively committed to different fates through a two-step process: specification followed by determination. Specification is demonstrated by removing a segment of an early embryo, “neutrally” culturing the tissue in vitro—for example, in a petri dish with simple medium—and then observing the derivatives. If the cultured region gives rise to cell types that it would normally generate in the embryo, this means that it is specified. In...
18.5K
TGF - β Signaling Pathway
7.4K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.4K
Master Transcription Regulators
6.9K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
6.9K
Bone Formation by Endochondral Ossification
4.5K
Bone formation, or ossification, begins around the sixth to seventh week of embryonic development. Most bones develop from a cartilaginous template through the process of endochondral ossification. Cartilage formation begins when clusters of mesenchymal cells differentiate into chondrocytes. These chondrocytes proliferate rapidly and secrete an extracellular matrix that becomes encased in a membrane called the perichondrium. The resulting cartilage model provides a template that resembles the...
4.5K
Bone Formation by Intramembranous Ossification
6.2K
Intramembranous ossification is one of the two processes involved in the development of bones within an embryo. The flat bones of the face, most of the cranial bones, and the clavicles are formed via this process. During intramembranous ossification, the bones develop directly from sheets of undifferentiated mesenchymal connective tissue.
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into ...
The process begins when mesenchymal cells in the embryonic skeleton gather together and differentiate into osteogenic cells, which then develop into ...
6.2K
Cooperative Binding of Transcription Regulators
2.0K
2.0K


