需要Hox10和Hox11基因才能在全球范围内塑造哺乳动物骨的模式
Deneen M Wellik1, Mario R Capecchi
1Howard Hughes Medical Institute and University of Utah, Salt Lake City, UT 84112, USA.
概括
在小鼠中破坏Hox10或Hox11基因揭示了它们在骨模式中的关键作用. 失去Hox10会阻碍腰椎的形成,而失去Hox11会影响十字椎的形成,影响轴骨的发育.
科学领域:
- 发育生物学 发展生物学
- 遗传学 是一个遗传学.
- 骨生物学 骨生物学
背景情况:
- 霍克斯基因是胚胎发育的关键调节者,控制沿前后轴的分段身份.
- 对于Hox10和Hox11对等组在轴向和附骨架图案中的特定作用仍然不完全理解,特别是在功能冗余方面.
研究的目的:
- 调查Hox10和Hox11基因家族在轴和尾骨架的模式中的全球作用.
- 阐明Hox10和Hox11对等组中的功能冗余性.
主要方法:
- 产生和分析具有被破坏的Hox10或Hox11对等组的小鼠.
- 骨结构的表型分析,专注于脊椎的身份和肋骨的形成.
主要成果:
- 霍克斯10功能的完全破坏导致腰椎缺失,并沿所有后椎形成肋骨.
- 霍克斯11功能的完全破坏导致了十字脊椎形成的失败,这些脊椎采用腰椎身份.
- 观察到显著的功能冗余,因为在6个相似基因中的5个基因突变的小鼠中,全球模式缺陷并不明显.
结论:
- 霍克斯10和霍克斯11基因在哺乳动物骨的全球模式中发挥着重要的,独特的作用.
- 类似的霍克斯基因之间的功能冗余可以掩盖个体基因对复杂发育过程的贡献.
相关概念视频
Bone Remodeling
Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.
Determination
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 contrast, determination...
Hedgehog Signaling Pathway
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
Bone Formation by Intramembranous Ossification
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...
Bone Remodeling and Repair
Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
Bone Formation by Endochondral Ossification
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...


