在肢体发育过程中,METTL14通过GDF5-RUNX-细胞外基因矩阵基因轴调节体发生
Nobuko Katoku-Kikyo1,2, Hiroko Kawakami1,2, Max Cantor1,2
1Stem Cell Institute, University of Minnesota, Minneapolis, MN, USA.
Nature communications
|April 30, 2025
概括
N-甲基氨酸 (m6A) RNA甲基化对体生成和四肢发育至关重要. 这项研究揭示了一个m6A驱动的级联调节软骨形成和骨模式.
科学领域:
- 发展生物学 发展生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- N-甲基氨酸 (m6A) RNA甲基化对于哺乳动物的发育至关重要.
- 在軟骨形成過程 - - 軟骨生成中,m6A的特定作用尚不清楚.
- 了解这些作用是解读骨发育机制的关键.
研究的目的:
- 调查m6ARNA甲基化在软体生成和四肢形态发生过程中的必要性.
- 在骨发育过程中识别由m6A调节的分子通路.
- 在肢体发育的背景下阐明Mettl14的功能.
主要方法:
- 产生特定于肢体祖先的淘汰赛小鼠缺乏Mettl14,这是m6A甲基转移酶复合体的关键组成部分.
- 在淘汰赛和野生类型小鼠中分析四肢形态和软骨原蛋白形成.
- 蛋白质组分析以确定差异表达的蛋白质和基因表达概况.
主要成果:
- Mettl14淘汰赛破坏了软骨的形成,导致四肢骨缩短.
- 确定了11种下调调节的蛋白质,这些蛋白质涉及体生成.
- 发现m6A可以稳定转录并增加GDF5,Runx2和Runx3的蛋白质水平,这些蛋白质是体生成的关键调节者.
- 这些因素随后促进了原基因和其他原因子的表达.
结论:
- 甲基RNA甲基化对于体生成和四肢骨发育至关重要.
- 一个新的m6A-依赖基因调节级联,涉及GDF5,Runx2/3和下游目标,控制着体生成.
- 这项研究揭示了一个关键的表观遗传机制,它是骨模式的基础.
相关概念视频
01:24Bone Formation by Endochondral Ossification
3.4K
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...
3.4K
01:07Development of the Limb Synovial Joints
1.2K
Joints form during embryonic development in conjunction with the formation and growth of the associated bones. The embryonic tissue that gives rise to all bones, cartilage, and connective tissues of the body is called mesenchyme.
The mesenchymal stem cells differentiate into chondrocytes that form the hyaline cartilage, and later the cartilaginous model of the bone. This model further transforms into a bone. This process is known as endochondral ossification.
During development, the limbs...
The mesenchymal stem cells differentiate into chondrocytes that form the hyaline cartilage, and later the cartilaginous model of the bone. This model further transforms into a bone. This process is known as endochondral ossification.
During development, the limbs...
1.2K
01:09Changes in the Appendicular Skeleton with Age
1.8K
The upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after.
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying...
1.8K
01:27Growth of Cartilage and Bone Tissue
2.9K
Chondrocytes form a temporary cartilaginous model by dividing and secreting a thick gel-like extracellular matrix. Once the chondrocytes undergo programmed cell death, osteoblasts enter the site of the cartilaginous model. The process of replacing the temporary cartilaginous model with bone in an ordered manner is called endochondral ossification. In endochondral ossification, not all of the cartilage is replaced by bone tissue. Some cartilage that performs a protective and supportive function...
2.9K
02:23Master Transcription Regulators
6.7K
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...
6.7K
01:16TGF - β Signaling Pathway
7.2K
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...
7.2K